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CRISPR: The Future of Medicine and Human Evolution

Humanity’s unnerving cruelty is perhaps only balanced by its kindness and innovation. It remains to be seen on which side of the scale CRISPR, a remarkable genome-editing tool and one of the most exciting scientific innovations of the 21st century, will land.

In their monumental 1953 Nature paper — stretching over little more than one glorious page and including only a simple diagrammatic illustration and a fuzzy x-ray image — Nobel laureates James Dewey Watson and Francis Harry Compton Crick proclaimed the following, “We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.” Of considerable biological interest, indeed, and a critical aspect of the discovery of CRISPR.

The Human Genome Project (HGP) taught us how to read long stretches of Watson and Crick’s miraculous DNA double-helix: it taught us how to read the code of life. CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) is the most recent step along the path towards absolute control over the human genome. CRISPR provides us with the ability to edit the code of life seemingly at will.

In the most basic of terms, CRISPR can recognize specific DNA sequences, using complementary guide RNA and recruit cutting-enzymes (e.g., the endonuclease Cas9), which precisely cut-out the targeted piece of genetic material. Under the right conditions, the cut region is subsequently “filled-in” with new DNA by the cell’s normal DNA-repair machinery.

The scientists to unlock the full genomic-editing potential of CRISPR (expanding on the work of numerous other great scientists), and likely future Nobel-laureates, Jennifer Doudna (Berkeley, California), Emmanuelle Charpentier (Max Planck Institute for Infection Biology, Berlin) and Feng Zhang (Broad MIT), published two papers in quick succession in 2012 and 2013, describing the remarkable capability of CRISPR to precisely and reliably (to varying degrees) edit the genomes of cells, including of mammalian cells.

The promise of CRISPR technology is highlighted by the contentious ongoing patent dispute between Berkley and Broad, to clarify who discovered what when and who holds the rights to technology estimated to be worth billions of dollars.

Why is this technology worth billions of dollars? For one, think about every genetic disease you have ever heard of. Did cystic fibrosis come to mind? Do you know anyone with Tay-Sachs Disease? Duchenne Muscular Dystrophy, going once, going twice, sold to the fastest gene-editor. In theory, by combining in vitro fertilization with CRISPR technology, every known hereditary single-gene disease (you may have noticed that the above examples are all generally caused by single gene mutations) can be eliminated. Not in a year from now. Not tomorrow. Today!

Chinese researchers have validated that CRISPR/Cas9 can be used to alter human embryos, and recently Kang et al. (The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China) used CRISPR to “cure” human embryos of beta-thalassemia and glucose-6-phosphate-dehydrogenase (G6PD) deficiency. The success rate (i.e., the percent of embryos that were successfully altered using CRISPR) varied significantly between studies, a concerning aspect of the technology that is likely going to be optimized rapidly, considering that CRISPR has only been in the scientific mainstream for a few short years.

Eradicating more complex diseases in embryos is a bit more complicated and will take some time. Editing genomes to treat cancer, for example, in mature individuals will also take a bit more time. However, the FDA approved a clinical trial in 2016 to test the potential of CRISPR as a tool to enhance the ability of immune cells — modified outside the body, similar to the idea of modifying embryos in vitro — to destroy cancer cells.

There are ethical challenges to consider. Luminaries like David Baltimore, Paul Berg and others have described these challenges in detail and have proposed appropriate steps to consider. Changes to the genome are of course permanent and as such are potentially passed on from generation to generation (i.e., changes made to an embryo are potentially passed on to subsequent offspring). Evolution at the speed of light if you will. Would it be possible to use CRISPR to create super-humans? To implant kill-switches into human cells? To prolong the lives of those that can pay for it?

The decision in February of 2016 by the UK Human Fertilisation and Embryology Authority (HFEA) to grant permission to UK researchers to edit the genome of human embryos is emblematic of the global embrace of CRISPR. Even in the US, a country generally less accommodating when it comes to research on human embryos, an international committee convened by the United States National Academy of Sciences (NAS) and the National Academy of Medicine concluded earlier this year that editing the DNA of a human embryo to prevent disease could be ethically permissible under the right set of circumstances.

If nothing else, history (Robert Oppenheimer’s opinion on the matter would be intriguing) has taught us that world-altering technologies like CRISPR cannot be un-invented. We all have front row seats to watch in awe as CRISPR transforms medicine, science and perhaps human evolution itself. Our best hope is to educate each other, to stay informed and to try to minimize the abuse of a tool powerful enough to re-write the code of life and the future of humanity.

Tim Beck (4 Posts)

Medical Student Editor Emeritus

Drexel University College of Medicine

I am an MD/PhD Candidate at Drexel University College of Medicine/Fox Chase Cancer Center. My research focuses on cancer cell signaling, drug resistance, cancer cell invasion and discovery of prognostic biomarkers. Politics (national and international), foreign affairs and healthcare policy are additional topics I am particularly interested in.