The extraordinary progress of molecular medicine has brought the promise of personalised, curative health care within unprecedented reach; to the extent that these advances are increasingly regarded as the Holy Grail of personalised medicine.

The questions of whether this field of medicine is indeed the Holy Grail or a poisoned chalice, was central to Prof Walter (Wattie) Janse van Rensburg, Professor in the Human Molecular Biology Unit at the University of the Free State (UFS) School of Biomedical Sciences, inaugural lecture on Wednesday (30 September). This inaugural lecture titled Holy Grail or Poisoned Chalice? Reflections on Molecular Medicine, Ethics, and Choice traced Prof Janse van Rensburg’s personal journey, reflecting on his experiences, challenges, and decisions that have shaped his life and academic career.

Prof Vasu Reddy, Deputy Vice-Chancellor: Research, Innovation and Postgraduate Studies, Prof Bulelwa Nguza-Mduba, Deputy Vice-Chancellor: People and Operations, together with Prof Chris Viljoen, Head of School of Biomedical Sciences and Acting Dean of the Faculty of Health Sciences, Dr Pieter du Toit, member of the UFS council, and Prof Jaco Joubert, Head of the School of Pathology, were amongst the attendees.

Prof Reddy, who oversaw this inaugural, remarked: “Prof Janse van Rensburg’s contribution invites us to imagine a future where innovation is guided by equity, care, and human dignity. Molecular medicine stands at the intersection of biology, genetics, biochemistry, and clinical practice, illustrating how collaboration across fields drives discovery and societal benefit. The distinction between the ‘Holy Grail’ and a ‘Poisoned Chalice’ is ultimately a question of responsible innovation. Excellence in science requires evidence, integrity, ethical reflection, and a commitment to ensuring that hope never outruns the science that supports it.”

The advancement of molecular medicine

“The advancement of molecular medicine has given us unprecedented power to rewrite the human genome; however, we have to acknowledge that sequencing a genome does not guarantee understanding of a disease; identifying a mutation does not guarantee a cure; and that editing a gene does not guarantee a healthy life. The true Holy Grail of molecular medicine is not merely the ability to identify mutations and manipulate genes.”

Prof Janse van Rensburg said: “Whether it becomes the Holy Grail of medicine or a poisoned chalice depends not on the technology itself, but on the wisdom, humility, and ethical principles that acknowledges the complexity of individual biology, recognising each individual as a beautifully woven, complex tapestry, and not only a book that needs correcting; it lies in our ability to temper optimism, ambition and arrogance with ethically sourced evidence; and to ensure that the hope the technology brings, never outruns the ethical science it is based on.”

At the beginning of his lecture, Prof Janse van Rensburg, a C2 NRF-rated researcher whose research focuses on the molecular causes of common health-related disorders, said he thought he had two career choices: a rugby player or a chef. However, all this changed when his stepfather, a diagnostic radiologist, saved a patient’s legs from amputation in a hospital in New Zeeland.

“From that day I knew this is what I want to do. But I knew I had to get the best training and that training is in Bloemfontein. In my grade 11 year, I returned to South Africa and later wanted to study medicine at Kovsies, but God decided otherwise. My counselling teacher advised me to include BMedSc Human Biology as a study option on my application forms. I was selected to study BMedSc, but the letter for medicine never came,” Prof Janse van Rensburg said.

Baking a cake

One of the highlights of his career, Prof Janse van Rensburg said, was helping to establish the safety and efficacy profile of a new drug called ALX-0681 which is used in the treatment of Thrombotic thrombocytopenic purpura (TTP); a rare, life-threatening blood disorder. At that stage, it had no formal pharmaceutical treatment available. The drug went on to clinical trials and is currently registered by the FDA in the US.

When all the drugs they tested after this success failed, Prof Janse van Rensburg went into molecular biology – almost starting from scratch. “I condensed it into something I could understand, with my love for cooking, I thought the perfect analogy was to see molecular biology as the steps to baking a cake. With the cells being the bookshelf with recipe books inside, the chromosomes being the books, the DNA being the language of the recipes, and the genes being the individual recipes. These recipes provide a blueprint to prepare the sequence of proteins, in this case, translate into the perfect cake.

“Therefore, in molecular biology, if you can read the recipe, you can determine how small differences in the recipe may result in different outcomes. We may end up with something that is not functional. We either understand the difference, try and manage the different or create new ingredients to address the difference,” Prof Janse van Rensburg explained.

After completing his PhD, he started focusing on molecular medicine – an interdisciplinary field, incorporating certain parts of molecular biology, genetics and biochemistry and use these tools to understand, diagnose and treat diseases at the molecular or cellular level.

Holy Grail vs Poisoned chalice

According to Prof Janse van Rensburg, there are many examples of how molecular medicine can be the Holy Grail. It enables the development of targeted therapies, with less side effects and increased quality of life. These medicines boost survival rates, progression-free survival, and response rates.

“We can avoid ineffective drugs which cuts unnecessary stress, hospital stays, and emotional burden on patients. We can also support prevention, have accurate risk assessment, and customised interventions which lead to better outcomes. It drives innovation with biomarker-driven drug-extending life expectancy.”

By using practical examples, he indicated how close researchers are to achieving the Holy Grail. Chronic Myeloid Leukaemia, he said, is caused by a single well-defined molecular abnormality, then came the miracle drug which targets the defect and became a standard therapy for newly diagnosed patients. These drugs increased the 10-year survival rate for patients from less than 20% in the early 2000s to over 90%. He also referred to a specialised molecular treatment that can now treat Sickle-Cell Anaemia, as well as the drug which has changed the lives of patients with Haemophilia A.

Referring to the poisoned chalice, Prof Janse van Rensburg said the challenges can be technical and include the high cost associated with molecular medicine. It inflates healthcare expenses without guaranteed benefits.

“It can also exacerbate inequities; favour high-income patients and regions, widening global health disparities. The molecular treatment for Sickle-Cell Anaemia is only available in North America, but Africans suffer the most from this disorder. We need African solutions, for African challenges. Overhype of molecular medicine leads to false expectations. The evidence has shown that molecular medicine has, in some cases, failed to show benefits, especially for complex diseases such as Alzheimer’s disease.

“Being located in Africa, we got logistical barriers with insufficient tissue samples and testing reliability. The lack of specialised equipment and expertise leads to increased specialist workload and burnout. Furthermore, molecular medicine is not universal. It overlooks common illnesses driven by lifestyle, luring patients into ineffective pursuits.”