Innovation From Animals And Evolution
By Ben Comer, Chief Editor, Life Science Leader
What do cephalopods, elephants, and round worms have in common? Each animal contains a biological insight that led to the launch of three biotech companies, each hoping to translate those insights into medicines that improve human health.
Cephalopods can change their physical characteristics, such as color and shape, due to a "plasticity in proteins” controlled by RNA changes, Ram Aiyar, Ph.D., CEO at Korro Bio, told me during this year’s J.P. Morgan Healthcare conference. Research into cephalopod RNA – combined with the emergence of CRISPR genetic editing – led the founders of Korro Bio to see an opportunity in RNA editing. Challenges associated with DNA editing reinforced the idea that RNA editing, which doesn’t require cutting into DNA, could be used to trigger biological changes on a transient basis, a concept that served as the genesis of the company, said Aiyar.
Elephants are the largest living land mammals; they can live for 70 or even 80 years, and yet, they rarely get cancer. Joshua Schiffman, MD, a cancer survivor, cofounder and CEO of Peel Therapeutics, told me that based on their size, elephants should be dropping dead from cancer before they even reach the age of reproduction. During a conference Schiffman attended on evolution and medicine 10 years ago, elephants came up, and an evolutionary biology researcher, Carlos Melay, described his finding that elephants have multiple copies of a gene (TP53) that produces the p53 protein – also known as the “guardian of the genome” – whereas humans and other mammals only have one copy of TP53. Schiffman cofounded Peel Therapeutics, a play on the Hebrew word for elephant, after connecting with cofounder Avi Schroeder, who was developing a nanotechnology-based drug delivery system. The company is in the discovery phase with a solid tumor candidate composed of lipid nanoparticles loaded with elephant p53 proteins.
Round worms were eradicated from the digestive systems of humans in industrialized nations just over 100 years ago – the same time that allergic and autoimmune diseases were first described. “If you look at diseases like Crohn’s, multiple sclerosis, and Type 1 diabetes, it’s the areas of the world that still have gut worms today that don’t get those diseases,” Andrea Choe, MD, Ph.D., cofounder and CEO of Holoclara, told me in January. Holoclara is working to synthesize the secretions and excretions of parasitic worms to create new drugs, potentially a more promising, or at least a more controlled approach, than patients reinfecting themselves with live parasites.
The concept of learning from evolution across expansive periods of time, and how the chemicals in our bodies have responded to that driving force, is catalyzing new research and new discoveries, in part due to the growing power of AI technologies. “The number of chemical experiments conducted by Nature is on a scale quadrillions-fold beyond human capabilities,” Empress CEO Jason Park recently told my colleague Wayne Koberstein. “In the past couple of years, the exponential growth of sequence data and computational tools like natural language processing has enabled us to better understand how DNA programs cells to synthesize chemistry.”
Last month, an article in Nature described findings from a dataset of over 1,600 ancient genomes taken from Mesolithic, Neolithic and Bronze Age human remains, which was then used to infer local ancestry tracts from samples in the U.K. Biobank. The results show that “risk alleles” for specific disease types, including diabetes and Alzheimer’s disease, differ according to different migration patterns and selection, and help explain phenotypic differences among contemporary Europeans. A better understanding of the evolutionary past, at the genetic level, promises to aid in the discovery and development of better drugs to treat intractable diseases.
The father of evolutionary biology, Charles Darwin, only made it through two years of medical school in Edinburgh before dropping out; it turned out that he preferred the outdoors, and the study of animals. Over 150 years after the publication of On the Origin of Species, the twin disciplines of medicine and animal evolution – assisted by emerging AI tools – are more conjoined than ever.