Next episode in NOTL library's online Nobel series is Monday, Nov. 22

For Frances Arnold, the question was how to design a better enzyme to break up plastic or perhaps create new drugs?

Frustrated by the daunting challenge of trying to build better enzymatic proteins from scratch, she had a better idea: why not harness evolution to get the job done.

It worked beautifully: after several rounds of introducing mutations into the gene coding for an enzyme, the enzyme became much more effective. For her achievement and approach, Arnold won a well-deserved Nobel Prize in 2018.

Two Nobel Prizes this year also spotlighted proteins. The chemistry prize was awarded to Benjamin List and David MacMillan for developing organic catalysts (enzymes), as tools for creating more effective drugs and other biologic compounds.

And the physiology-medicine prize went to David Julius and Arden Patapoutian for identifying specific types of protein receptors, which translate touch, temperature, pain, muscle, and tendon sensations into electrical signals, to provide the brain with a running account of what’s happening to the skin and deeper tissues.

Roles as enzymes and sensory receptors are only two of thousands of jobs proteins do. For example, each cell has its own complex cytoskeleton comprised of tubules and filaments of various sizes.

They buttress the cell wall, change the shape of some cells, anchor organelles within the cytoplasm, provide an internal mail delivery service for molecules, in addition to playing key roles in the activation or silencing of genes and important roles in cell division, and in the case of muscle fibres, are the proteins that ratchet pass one another to shorten the fibres and generate force.

Proteins are produced by genes. To make the protein specified by a gene, the first step is to create a single-stranded copy of the gene in a process called transcription. This creates messenger RNA (mRNA), whose sequence of bases matches that of the original gene except for the RNA copy, in which the base uracil substitutes for the base thymine in DNA.

In structures called ribosomes, located in the cytoplasm, the mRNA is read sequentially, three bases at a time, to specify which of 20 amino acids is next in line to be added to the growing protein chain, in a process called translation.

The process from transcription to translation is complex and sometimes problems occur. For example, if the gene is mutated in a way that disables the protein, loss of the function of that encoding gene and its protein product may occur, which in many inherited diseases, may be serious.

For example, in Huntington’s disease, long strings of the same amino acid glutamate occur, or in the case of myotonic dystrophy, long strings of leucine may develop, which badly distort the shape and therefore the function of the protein involved.

Unfortunately, the latter leads to death of many of the brain cells in Huntington’s disease and disordered function or death of muscle fibres, and in some instances loss of brain cells, in myotonic dystrophy.

Last year a Nobel Prize was awarded to Jennifer Doudna and Emmanuelle Charpentier for their discovery of the CRISPR-Cas system for editing genes.

The method is clever, precise and much easier to work with compared to earlier methods for editing genes and spawned enormous interest in treating many otherwise intractable hereditary diseases that usually cause problems through a loss of function in a mutant gene’s product, the corresponding version of a protein.

Fixing heritable diseases with CRISPR-Cas isn’t without its problems, what with off-target hits on other genes and sometimes activating oncogenes, tragically leading to cancer. The other challenge is ferrying the CRISPR-Cas fix to the intended target cells in the bone marrow, liver, brain or other sites, without affecting other tissues or organs.

Fortunately, the tamed viruses tasked with ferrying the CRISPR-Cas have been engineered to home in on the target tissue, with little or no collateral spread to other tissues.

My guess is that the CRISPR-Cas method for editing genes will prove to be an effective, safe method for treating many hereditary diseases within the next two decades. This revolutionary technology began with studying the immune system of bacteria as they fend off viruses. If we ever needed an argument for supporting basic sciences and what at first might seem esoteric studies, here’s one.

*The next talk in the Nobel lecture series, on sensation and proteins, is scheduled for Monday, Nov. 22 at 11 a.m. If you're interested, sign up with the NOTL Public Library online or contact Debbie Krauss, without whom there might not be a program. Honest!

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.