Chemistry Bonding with Medicine: New Pathways for Prevalent Diseases

The modern-day fields of medicine and chemistry are fused as never before, which is also evident in Nobel prizes, where doctors often receive the prize in Chemistry and chemists become Laureates of Physiology or Medicine. This year’s Lindau Nobel Laureate Meeting is dedicated to chemistry, but it wouldn’t be complete without the contribution of two Nobel Laureates in Physiology or Medicine and two medical doctors, who are Nobel Laureates in Chemistry. All are actively finding ways to try and curb the world’s most prevalent diseases.

Parasites

Nearly 20 years ago, Peter Agre was awarded the Nobel Prize in Chemistry for the discovery of aquaporin-1, a membrane water channel. But since 2008, Agre has served as Director of the Johns Hopkins Malaria Research Institute, and in this position he’s able to connect research on aquaporins and a global health problem, which first caught his attention as a young backpacker in Asia.

Aquaglyceroporins enable solute transport through cell membranes, and this has implications for infection with malaria; without these transporters, the Plasmodium parasite, injected into the bloodstream by an Anopheles mosquito, wouldn’t be able to proliferate in liver cells. The aquaglyceroporin-deficient parasite is less virulent, yet still sufficiently virulent to cause malaria. „We don’t think it’s a drug target, but that’s research,“ said Agre.

Malaria kills over half a million people each year, the majority of which are children under five in Sub-Saharan Africa. „Malaria is a disease that we can take care of if the resources are available,“ noted Agre, further highlighting the complexities of minimising malaria burden−organisation mismanagement leading to wasted resources. Agre concluded his talk by giving words of hope to the young scientists in the audience: „It’s very easy to be discouraged in this business. Look to the future; the future is you young scientists (…). You never know with science, what’s around the corner.“

Cancer

„Mr Kaelin appears to be a bright young man whose future lies outside the laboratory,“ wrote William G. Kaelin, Jr.’s chemistry professor in his senior year at college. „The project I was given was uninteresting, unimportant and undoable,“ recalled Kaelin, but fortunately it didn’t dampen his enthusiasm for lab work later on.

Kaelin received the Nobel Prize in Physiology or Medicine in 2019, along with Sir Peter J. Ratcliffe and Gregg L. Semenza „for their discoveries of how cells sense and adapt to oxygen availability.“ His independent research career centred around Von Hippel-Lindau disease (VHL), a rare hereditary tumour-suppressor disease, which causes different types of cancer, particularly clear cell renal cell carcinoma, the most common form of kidney cancer.

VHL-associated tumours induce blood vessel formation and increase red blood cell production, which is linked to oxygen sensing. By figuring out how the oxygen-regulated machinery makes cancer cells grow, pharmaceutical companies were then able to produce new anti-cancer therapies, including belzutifan, the first drug for VHL-associated kidney cancer. „Of course the (Nobel) prize is wonderful,“ said Kaelin, „but there’s something special also when you can see that what you’re working on, if you’re very, very lucky, occasionally touches people and improves their lives.“

Neurodegenerative Disorder

„I’m on a steep learning curve,“ said Randy Schekman during his lecture on Parkinson’s disease (PD). The 2013 Nobel Prize Laureate in Physiology or Medicine spent many years looking at vesicle transport in the cell, but personal loss gave rise to a new research interest. Schekman lost his wife to PD in 2017. Soon after, he was approached by Google co-founder Sergey Brin, who is a carrier of the gene mutation responsible for PD and „has an enlightened self-interest in the development of treatment,“ Schekman explained.

There is a pandemic of Parkinson’s disease, with over 10 million people worldwide living with the condition and millions more will be diagnosed in the coming years. Unfortunately, little can be done to help them. „In the last several decades we’ve enjoyed tremendous progress in the major killers, cancer and heart disease,“ said Schekman, „but with the scourge of neurodegenerative disease, there have been no treatments.“

Schekman is Scientific Director for asap (Aligining Science Across Parkinson’s), which is supported by the Sergey Brin Family Foundation. The program brings basic scientists from around the world in a collaborative effort „to finally crack the code of this scourge of humanity,” concluded Schekman.

Viruses

Aaron Ciechanover, who won the Nobel Prize in Chemistry in 2004, gave his lecture on the COVID-19 pandemic and the many „bioethical bumps“ that arose with this international health emergency.

The primary ethical issue faced by hospitals worldwide was priority of treatment − who gets to be treated first, and how can medical staff decide who will receive treatment and who won’t? Another problem that the pandemic brought forward was prioritising the disease itself, at the same time neglecting patients with other diseases. „Is the cancer patient less important than the corona patient?“ asked Ciechanover. This approach also spilled over into other walks of life. „Many decisions were postponed,“ said Ciechanover, „including on climate change.“

Vaccine scepticism was a central part of Ciechanover’s lecture, and for some of the roots of this occurrence, „we have to look in the mirror, at ourselves.“ This ethical issue is closely associated with the infodemic and the spread of disinformation. Ciechanover described the grim outcome of linking the MMR vaccine to autism and the refusal to take the HPV vaccine by many Japanese women.

The COVID-19 pandemic brought into focus many aspects related to health and disease, but also general problems in society-inequality and discrimination. „Gender medicine is an interesting, newly-evolving area,“ explained Ciechanover, providing the example of the focus on male participants in clinical trials (and even male mice in the laboratory!), which could lead to poorer health outcomes for women.

We still don’t know what the future holds for the coronavirus pandemic. But if there’s any silver lining in this public health crisis, it’s perhaps the fact that many sensitive issues have been exposed and must be dealt with in order to move forward. These problems are now „sitting on our table,“  said Ciechanover.