Malaria, Vaccines and the Riddle of Steel

In the 1982 movie “Conan the Barbarian”, the title character is told by his father (a blacksmith) that he must learn “the riddle of steel”. Conan’s father is then slain by the villain who then tries himself to understand the riddle which he abandons when he realises “flesh is stronger than steel. In the end the broken sword allows the hero to break free from the villains mind control.

The morale of the story is that the riddle of steel is less about the question and answer but about what the question is in the first place.

Here I’d like to posit that a movie where a young Arnold Schwarzenegger strides around in a loincloth and fights a bewigged James Earl Jones has useful implications for biotechnological and drug development in Africa. Because the riddle of steel is less about being posed a problem and answering it, and more about deciding what the question is in the first place and then following all the twists and turns of unlocking the answer for yourself. This brings us to malaria.

Biotechnological and drug development in Africa has always been a conundrum especially when it comes to malaria.

Malaria is one of those tropical diseases that seems tailor-made to exacerbate every form of human suffering. It kills the young and infirm, weakens the survivors, recurs again and again over the course of its progression, slows economic development and generally makes life worse for hundreds of millions of people. Even our adaptions to fight the parasite are problematic, with genetic conditions such as sickle cell anaemia providing some protection for carriers of the gene but cursing those who get both recessive copies to a laundry-list of terrible symptoms.

So the announcement, in April 2021, that a vaccine had been tested in Burkina Faso which demonstrated 77% efficacy, should bring general rejoicing. This vaccine is a collaborative effort between the University of Oxford, the KEMRI Wellcome Trust, the London School of Hygiene and Tropical Medicine, the Serum Institute of India, the Institut de Recherche en Sciences de la Santé, and a private company called Novavax.

It makes use of a known malarial protein antigen and an adjuvant called “Matrix-M™”. Matrix-M, as it currently exists, is made from a mixture of saponins derived from the Chilean Soapbark tree, along with cholesterol and phospholipids. This mixture is then processed to produce a solution of nano-particles which, when mixed with the antigen, both enhances the immune response and tailors its effects.

Novavax is the maker of Matrix-M, and has been working on something like it for a while now. Their portfolio of patents includes a ring of patents from 2014 that makes use of soapbark saponins as adjuvants. Interestingly, it seems that the improvement claimed by the patent rests partly on making use of a fraction of the saponins (i.e.: separating the soap-bark extract to identify a portion of the compounds with the best effects), which are then mixed with another adjuvant. This patent ring, along with another from 2014 directed toward the use of soapbark saponins in a vaccine formulation containing live microbes, has been followed up over the years with further patents directed towards influenza vaccines, MERS vaccines and, most recently, their successful Coronavirus vaccine.

Along the way to all the good news regarding Coronavirus and Malaria, the company has had some notable flops. For instance, a 2016 phase three trial of a product called ResVax, directed towards respiratory syncytial virus, failed hard and nearly took the company with it. This resulted in layoffs and a refocusing of the company’s efforts in 2017 – an effort which only bore financial fruit recently.

When we talk about biotechnological and drug development in Africa, there is often a focus on needs and metrics – an assumption that if enough IP is produced and enough start-ups spun off in a particular field, then successful solutions for local problems will emerge in a sort of programmatic fashion. What the story of Novavax’s involvement in the malaria vaccine shows is that such success is a lot more contingent and idiosyncratic than that. Each company, perhaps each technology, needs to set and solve its own riddle of steel to arrive at success.