Yeast is Humankind’s oldest friend

Leland Hartwell, PhD

Throughoutits evolution, the Homo sapiens species has been closely linked to several other forms of life, which we have modified, but also depend on for our own survival. I could be referring to wild animals that have been domesticated, or plants that originated from agriculture. However, the species that shares the strongest connection with us is Saccharomyces cerevisiae. This type of fungus shaped the development of society and culture as we know it, and in recent years has even been the object of remarkable scientific works, as is the case with AIMS 2023’s Nobel Lecturer, Dr. Leland Hartwell.

You may know it as “baker’s yeast”, because its fermentation has allowed us to make bread for millenia. In fact, the first known records of humans using it for this purpose comes from 1300 B.C. in ancient Egypt, while its use for beer brewing and wine-making has been observed in archeological findings in Sumeria and Babylonia from around 6000 BCE. Yeast has been known and used worldwide since approximately 170 BCE. In 1857, Louis Pasteur discovered that this was the agent responsible for alcoholic fermentation, turning carbohydrates into alcohol and carbon dioxide. Later, were described two forms of yeast cells, with sexual or asexual reproduction, either way undergoing a life cycle of mitosis and growth. Under conditions of stress, haploid asexual cells end up dying, while diploid cells can enter meiosis, a process that results in four haploid spores, each with one set of genes, which can subsequently mate.

According to Dr. Lee Hartwell, yeast “smells good”. But why has it remained so scientifically relevant? This single celled, easily cultured organism has a rapid generation time, doubling its population in 1,5 to 2 hours. Being an eukaryotic cell, the intracellular processes that occur are relatively similar to those that happen in humans, which means yeast could be used as a model organism. It has 16 chromosomes that comprise 6,000 genes, with roughly a third of them having survived with relatively little alteration over the one billion years of evolution that separate humans and yeast.

Lee Hartwell first studied at the California Institute of Technology, soon becoming interested in developing a research career. He then moved to Massachusetts, having received his Ph.D. from MIT in 1964. In 1968, he moved to the University of Washington where he developed a series of genetic and biochemical methods in order to study S. cerevisiae over the following four years. He discovered genes that encode for cyclin and cyclin-dependent kinase, molecules involved in the control of cell division Hartwell found that in response either to nutrients or to a cell that they are going to mate with, when yeast cells receive damage, they stop dividing and repair the damage. This point of arrest prior to DNA replication is what we know as G1, as in “gap”. Similarly, when human cells are not dividing, they may sit in this G1 for years before they get a signal to divide. This control mechanism recognizes damage and prevents it from transmitting it to daughter cells.

Hartwell recognizes he’s always been motivated to better understand certain aspects of cancer. In 1996, he joined the Fred Hutchinson Cancer Research Center in Seattle, Washington, having served as president and director. In 2009, he was a founding member and chief scientist of the Center for Sustainable Health at Arizona State University. Thanks to his breakthrough research, we now know that the genetic instability of cancer cells leads to mutations in the genes that control cell division and allow the transmission of damaged DNA. Tumor cells have small specific genetic mutations that have implications for cancer diagnosis. Targeted therapy for each patient has recently been a reality, improving overall outcomes of cancer therapy. Professor Hartwell’s work in the field of genetics has proven essential to understanding the promotion and regulation of the cell cycle. And to think all of this has been made possible with the same organism used for ancestral production of bread and alcoholic beverages…