Only one out of 10000 molecules finally makes it into a medicine. The development of any drug is an uphill struggle taking years to complete.
Published on 07/09/2023
Not a generation ago, the landscape was utterly grim. The need for optimism was obvious. But daring to say so was tantamount to hubris. Or worse.
The word cancer triggered such terror that just hearing it would make people turn pale. It was synonymous with agony. Even as modern medicine had developed treatments for some forms of the disease, its most potent tool – chemotherapy – was associated with equal horror due to its side effects.
By the 1980s, the situation was considered so dire that some pharma companies closed their oncology research. Among them was Novartis predecessor Ciba-Geigy, which discontinued its oncology activities for lack of convincing results.
The bleak outlook came despite major advances in the industry: Besides the development of the first chemotherapies during the Second World War when researchers found that mustard gas had a moderating effect on some cancers, scientists also hit upon the first gene that stood in a direct causal chain with a specific kind of blood cancer.
Luckily, the medical community was not left alone with the problem. Among widespread efforts to fight the disease, top policy makers also joined the fight against cancer, pouring billions of dollars into research and improved care. Among the first was US President Richard Nixon, who launched a nationwide cancer program that was picked up in other countries too. Later, US Presidents Bill Clinton and Barack Obama would launch similar efforts.
A new beginning
By the mid-1980s, Ciba-Geigy, among many others, made a fresh attempt at tackling cancer, hiring several young and extremely motivated researchers, including Peter Dukor and Alex Matter, who wanted to change the course of cancer research and end the plight of millions of patients.
Although many doubted that this endeavor would lead to a tangible result, the team kept on toiling, zeroing in on so-called kinases, a type of enzyme, which at that time were little understood but which some thought could help in finding new treatment options for cancer patients.
Despite the challenge, Matter and his team remained totally dedicated. They believed that the targeted manipulation of kinases would lead to progress, especially in leukemia. Previous research had shown that chronic myeloid leukemia was triggered by a gene defect that prevents the switching function controlled by a specific kinase from being carried out correctly.
The problem, however, was finding a chemical key to switch off the protein that triggered the disease without affecting the other switches. This was a task that Matter assigned to a young and aspiring scientist: Juerg Zimmermann.
“When Alex came to me and asked if I’d like to work on this problem, I was immediately interested,” Zimmermann, who has since retired, told live magazine back in 2016. “It was a problem similar to the one I had had to solve for my diploma thesis at the ETH, when I wanted to solve the question of how life sprang from a single molecule. It was a problem in which I could fully immerse myself.”
However, the search for a molecule proved to be extremely difficult and time-consuming. Zimmermann took very few breaks and worked almost without interruption, including many weekends. But finally, he found the key and synthesized a molecule that influenced precisely the mechanism that triggered leukemia. “It was an extremely intensive period during which I paid too little attention to separating my private life from my work,” says Zimmermann in recollection of the early 1990s when he started his career at Ciba-Geigy at the age of 33. “Of course, with the experience I have today I would do things differently.”
A courageous mindset
To the surprise of almost everyone, the frantic research efforts led not only to a potent cancer treatment. The drug, which would become the first treatment to target a molecular defect, would change the course of cancer science because the new treatment showed that the disease could now be effectively addressed without exposing patients to the harmful side effects commonly associated with chemotherapy.
The effort to understand the underlying cause of the disease and follow its genetic and molecular path while seeking a solution to inhibit the disease-causing mechanism was also clear proof that so-called rational drug design was a feasible avenue in the perennially challenging oncology arena. This triggered new hope that cancer could be brought under control.
But while Zimmerman’s hard work was instrumental in developing the drug, the advance that came out of the Novartis labs was not just a lucky strike. It was the result of courageous steps and the result of a long-term research and development engagement, which the company started to intensify around the turn of the millennium.
Around the year 2000, the company created the Novartis Institutes for BioMedical Research (NIBR), the Novartis Institute for Tropical Diseases and the Genomics Institute of the Novartis Research Foundation, which is now part of NIBR. It not only hired hundreds of new scientists. It also established research campuses in Basel, Cambridge, San Diego and later in Emeryville.
The company also continually upped its research and development investments, which grew from around 2 billion US dollars in 1996 to more than 9 billion US dollars in 2022, helping Novartis develop breakthrough medicines in such diverse areas as oncology, inflammatory diseases and neurology.
