Few can boast about discovering a new DNA building block. Piet Borst, a physician-biochemist and molecular biologist who is currently an honorary staff member at the Netherlands Cancer Institute, achieved so, together with his colleagues, when he found base J, a modified version of thymine only observed so far in trypanosomes and its other parasitic relatives (1). And, not only that, he has achieved multiple notable breakthroughs: He helped reveal how the trypanosomes that cause sleeping sickness escape the human immune response, unveiled a mitochondrial metabolic transport route — the malate-aspartate shuttle, also known as the Borst cycle — and discovered novel insights into the mechanisms of drug resistance in cancer cells (2-4).

For his “exceptional 50-year career of scientific discovery, mentorship, and leadership,” Borst has been recognized today with one of the highest honors for medical research, the Lasker~Koshland Special Achievement Award.

I was extremely lucky that I was born in the golden age of biology and then managed to get into a career where there was still money for fundamental research. 
- Piet Borst, Netherlands Cancer Institute 

“Luck” and “accident” are some of the words Borst uses to describe his career. “Nothing of my career was planned,” he said. “The common thread is that I liked the projects I was working on, and usually by accident, I would start a new project,” he said. “I was extremely lucky that I was born in the golden age of biology and then managed to get into a career where there was still money for fundamental research.”

One of his most influential research areas is the study of molecular transporters, especially those involved in pumping drugs out of cancer cells, which contribute to cancer drug resistance. Together with his colleagues, he identified and characterized various members of the multidrug resistance-associated protein (MRP) family and developed the first mouse tumor model to facilitate the study of cancer cell resistance (5-7). 

Borst is one of the top scientists in the drug resistance field, said Zhe-Sheng Chen, a pharmacologist at St. John’s University. Borst is a pioneer in many senses, Chen said, because of his several discoveries on MRPs’ function, including his work associating MRP5 to increased resistance to a leukemia treatment (8). 

Chen also highlighted Borst’s qualities as a mentor. “In the conferences, he always encourages young generations in the field,” said Chen, who has not collaborated with Borst but has interacted with him throughout his career. “I learned a lot from him,” he added, and Borst’s attitude has inspired Chen to do the same with the new generations of researchers, he said. 

Borst said, “it’s a tremendous honor” to receive this award. “The gallery of people who have received it is absolutely stunning . . . and I feel extremely honored to be part of that gallery.”

References

1. Gommers-Ampt, J.H. et al. β-d-glucosyl-hydroxymethyluracil: A novel modified base present in the DNA of the parasitic protozoan T. brucei. Cell  75, 1129-36 (1993).
2. Hoeimakers, J.H.J. et al. Novel expression-linked copies of the genes for variant surface antigens in trypanosomes. Nature  284, 78-80 (1980). 
3. Borst, P. The malate–aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway. IUMBM Life  72, 2241-2259 (2020). 
4. Borst, P. et al. A Family of Drug Transporters: the Multidrug Resistance-Associated Proteins. J Natl Cancer Inst  92, 1295-302 (2000). 
5. Kool, M. et al. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res  57, 3537-47 (1997). 
6. Kool, M. et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci U S A  96, 6914-9 (1999). 
7. Rottenberg, S. et al. Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer. Proc Natl Acad Sci U S A  104, 12117-22 (2007). 
8. Wijnholds, J. et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc Natl Acad Sci U S A  97, 7476-81 (2000).