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CRISPR Rewrites the Very Molecules of Life

3 July 2017
Giulio Prisco

DNA Bricks

The cut-and-paste gene editing technique CRISPR has been all over the scientific news for a while, and seems poised to revolutionize all biotech sectors. “Clustered regularly interspaced short palindromic repeats” doesn’t sound too layman-friendly, but the recently published book, A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, co-authored by Jennifer Doudna, one of the inventors of the technique, is a fascinating read for everyone.

The book will tell you the story of one of the most important scientific discoveries of our time in understandable terms, and you’ll learn a lot of modern biotech along the way, ending with a simple wrap-up explanation of CRISPR to a class of sixth-graders.

With CRISPR, an organism’s entire DNA content “has become almost as editable as a simple piece of text,” explains Doudna (the two authors have agreed to use Doudna’s voice). "Scientists can use CRISPR to insert, edit, or delete the associated gene in virtually any living plant’s or animal’s genome."

The book is a page turner. The first two parts are packed with the history, science, and awesome applications of CRISPR, but in the last part Doudna doesn’t escape delving into the bioethical aspects of a technology that, besides curing disease, could open the door to inheritable genetic modifications in humans.

"As I write this, the world around us is being revolutionized by CRISPR, whether we’re ready for it or not," notes Doudna. "Within a few decades, we might well have genetically engineered pigs that can serve as human organ donors - but we could also have woolly mammoths, winged lizards, and unicorns. No, I am not kidding."

In fact, geneticists are using CRISPR "to transform Asian elephant DNA into something that looks more and more like woolly mammoth DNA, with the hope of someday resurrecting this extinct beast."

MIT Technology Review reports that Peter Thiel is funding efforts to resurrect the woolly mammoth led by Harvard University genomics expert George Church, whose research team is genetically modifying elephant cells with DNA retrieved from frozen mammoths. Of course, they are using CRISPR.

This will certainly bring up bioethical debates. Doudna reports that, "instead of creating red tape or introducing prohibitive regulations, [Steven Pinker] argued that 'the primary moral goal for today's bioethics can be summarized in a single sentence. Get out of the way.'" Giving a source for this position seems, to me, a clever way for Doudna to say the same with plausible deniability. I totally agree: regulators and bioethicists should get out the way and let scientists find out how life works and how we could make it work better.

"CRISPR gives us the power to radically and irreversibly alter the biosphere that we inhabit by providing a way to rewrite the very molecules of life any way we wish," is one of Doudna’s conclusions. "It won’t be long before CRISPR allows us to bend nature to our will in the way that humans have dreamed of since prehistory."

One of the key meetings in the history of CRISPR took place in the Free Speech Movement Café at the Berkeley campus. Due to recent political debates, I felt the need to check if the Café is still there. It is.

A recent review titled "Is CRISPR Gene Editing Moving Ahead Too Quickly?" warns that some research results cast doubts on the safety and precision of CRISPR. But research is in the works to make CRISPR safer and more precise, as shown below.

CRISPR mechanics captured at atomic level in supercomputer simulations. A team led by UCSD researchers, using a new molecular dynamics technique, shed light on the biophysical details governing the atomic-level mechanics of CRISPR-Cas9, the innovative gene-splicing technology that’s transforming the field of genetic engineering. In two research papers published in PNAS and ACS Central Science, the scientists describe new simulations performed at the San Diego Supercomputing Center (SDSC) with a new technique dubbed “Gaussian accelerated molecular dynamics” (GMAD), which works over longer times and permits capturing more complex biophysical and structural transitions. According to the scientists, the new research could open the way to overcoming the limitations of current CRISPR-Cas9 technology.

CRISPR mechanics captured at atomic level in the lab. Moving from supercomputer simulations to actual physical imaging in the lab, Harvard Medical School and Cornell University scientists have generated near-atomic resolution snapshots of CRISPR that reveal key steps in its mechanism of action. The research results, published in Cell, document how the researchers used a combination of biochemical techniques and cryo-electron microscopy, and provide the structural data necessary for efforts to improve the efficiency and accuracy of CRISPR for biomedical applications.

A spell-checker for CRISPR. Scientists at the University of Texas at Austin have developed a technique that can spot editing mistakes in the application of CRISPR technology to an individual’s genome. The study, published in Cell, describes ways to rapidly test a CRISPR molecule across a person’s entire genome to foresee other DNA segments it might interact with besides its target. According to the researchers, this new method could one day help doctors to develop personalized CRISPR gene therapies for individual patients, ensuring safety and effectiveness.

Potato virus nanoparticles against cancer. Scientists at Case Western Reserve University School of Medicine, Dartmouth Geisel School of Medicine, and RWTH Aachen University, have shown that injecting potato virus nanoparticles into melanoma tumor sites activates an anti-tumor immune system response in lab mice, and adding chemotherapy drug doxorubicin into tumor sites further helps to slow down tumor progression. Surprisingly, as shown by the research results published in Nano Letters, administering separate injections is as effective as injecting combined nanoparticles where the drug is attached to the virus.

Rejuvenating immune cells to combat cancer and viral infections. Immunologists at St. Jude Children's Research Hospital have discovered how immune cells called "T cells" become “exhausted” and unable to do their jobs of attacking invaders such as cancer cells or viruses. The study, published in Cell, also shows that a chemotherapy drug already in use, called decitabine, can reverse that exhaustion of immune cells.

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