Medicine’s Really Big Deal

Take a really good look at the two women above. Together, using breakthroughs like the completion of the human genome map, they may have opened the door to one of the most significant scientific inventions since antibiotics. An international team of sheer brilliance, the American biochemist Jennifer A. Doudna (left) and French microbiologist Emmanuelle Charpentier (right) won the Nobel Prize for Chemistry in 2020. Simply, they were awarded this prize for “rewriting the code of life.”  CRISPR. The ability to edit and reprogram genetic code, gene sequencing, a tool that provides infinite variety to address curing diseases, genetic abnormalities and extending life itself. Often referred to as medicine’s golden scissors.

“Officially, CRISPR refers to a DNA sequence found in bacteria called ‘clustered regularly interspaced short palindromic repeats.’ But the term has come to represent a process that lets scientists snip out genes in DNA as if they were snags in a strand of yarn. Scientists use a kind of RNA to find offending genetic code and a protein called Cas-9 cuts it out. Guide RNA then puts in a new set of code where the snag was, changing the original DNA sequence. The discovery has given scientists a way to reprogram life.” Ruth Reader writing for the March 16th FastCompany.com.

Without CRISPR, where a genetic model of the shape of the SARS-CoV-2 (COVID-19) becomes a teaching tool to our own immune defensive T-cells so the body can attack this horrific invader, none of the current vaccines against the virus would exist today. For details on each of the major vaccines available today, please look at my March 11th Attacking the Spike Proteins blog. From the time that the shape of a toxic virus can be created, it takes literally a couple of days to create the vaccine! The rest of the time is consumed with testing. And while these vaccines represent the first widespread use of CRISPR in the manufacture of a disease-preventing inoculation, this is just the tip of the iceberg. We are learning. There are still challenges and cost barriers, but the door to genetic innovation is opening fast.

For example, researchers looking at cancer victims and people with pre-programmed genetic disorders are drilling down on CRISPR’s potential, now that its first widespread “test” has proven so effective. Here is just one innovation that parallels a path that CRISPR has inspired: “[Medical technology company,] Inscripta’s Onyx—a ‘labtop’ gene editor—could democratize an array of breakthroughs promised by CRISPR technology… [It is] a compact gene editor that can make thousands of changes to genomes in millions of cells for $347,000. The initial device will edit yeast and E Coli, but it eventually promises to make large scale gene-altering a reality even in mammalian cells…” Reader. 

That may sound like an insurmountable cost, but for major hospitals and medical schools and research centers, it is quite reasonable. The most interesting aspect of this technology, one that is going to challenge the existing FDA approval process that generally requires economics of massive scale to justify the prohibitive cost of testing, is the ability to create targeted “solutions” to anomalies and limited-reach infectious diseases. Small pockets of pain and suffering that never justified the investment in cures and prevention. And so much more.

 “What could gene editing yield? The list of possibilities is truly endless, but at a minimum it could pave the way for new types of energy and food, as well as unique ways to fight disease… But CRISPR still has limitations. It can make the same repair in lots of different places or it can make several different repairs in one place, but it cannot do both at the same time. CRISPR can also be expensive to license commercially.

“For these reasons, Inscripta doesn’t use CRISPR Cas-9. Its scientists use proteins that act in similar ways, but are proprietary to the company, which charges a 3% licensing fee to commercial users. The goal of the technology is to make biological research as easy as doing a Google search…

“Andrew Garst joined Ryan T. Gill’s Lab at University of Colorado as a [post-doctoral researcher] in 2012… [Two years later, he] made a broad… realization. Instead of bombarding the cell with multiple sets of instructions carried on different RNA strands, he could synthesize the changes he wanted before inserting them into the cell, leading to a more highly efficient integration. This epiphany could make CRISPR useful at a much larger scale.

“Two years later, he published a paper detailing a way to use CRISPR to introduce as many as 500,000 changes to the structure of a genome at the same time. His design made these changes trackable. The paper also included computer code to help researchers reverse engineer the genetic coding in order to get a cell to do what they wanted it to do. The technique was called CREATE, which is shorthand for CRISPR-enabled Trackable Genome Engineering Using Homologous Recombination…

“Seeing the opportunity, Garst co-founded Inscripta around the time the paper was released, hoping to refine the CREATE technology into a more automated system… Over the last four years, Inscripta has company raised $300 million. In October, it hired a new CEO, Sri Kosaraju, who spent 16 years overseeing JPMorgan’s healthcare and technology portfolio, to scale the business. It also launched the Onyx benchtop: a black box roughly the size of a small fish tank with a computer screen front. It’s as slick looking as any digital consumer product, but made for scientists, with an interface that lets them create their experiments. Onyx’s software is designed to then optimize tests for the best possible results… Inscripta has shifted away from using CRISPR Cas-9 to develop its own proprietary DNA cutting nucleases. (As the name “Cas-9” implies, the Cas protein is one of many.)” Reader. 

With its 3% commercial licensing fee, Inscripta is hoping to become ubiquitous in the field. But there are dozens of biotech companies launching CRISPR driven research into new applications and process refinements. Ethical and biosecurity issues have also reared their ugly heads; the ability to create and counter biological weapons is obvious. “This scale of editing also raises questions about what kinds of mutants this technology may ultimately bear. What does democratizing this kind of technology mean for the safety of human health? Just as the automated assembly line can be made to produce cars, it can also be made to produce guns.

“This issue was the subject of a joint hearing on biosecurity convened by both the House Armed Services subcommittee and House Foreign Affairs subcommittee in October. Six committee members sat more than six feet apart at their elevated wooden desk. Ami Bera, a silver haired doctor and representative for California’s 7th District, chaired the meeting.

“‘We’ve not had an aircraft carrier brought to its knee by kinetic force of missile, but what we just saw in this past year was an aircraft carrier brought to port because of a virus—that really underscores what I worry about,’ said Bera. ‘The availability of technologies to alter viruses and do genetic editing, the know-how, and the capabilities are rapidly increasing and that is something that keeps me awake at night.’” Reader. Whatever else is said and done, medical research will never be the same.

I’m Peter Dekom, and this little backstory may someday become a personal medical moment that just might save your own life.