“My life needs editing.” —Mort Sahl
My commute to work in the Washington, DC, area is hell, to put it mildly. According to U.S. News and World Report, in 2015, Washington area drivers spent 75 hours on average in traffic, second only to Los Angeles drivers who averaged 81. I resemble this statistic and can testify that I spend entirely too much time doing an automobile version of a slow conga line to and from work. Needless to say, I have plenty of time to kill during my mind-numbing commute, and I have developed numerous strategies to pass the time at 10-15 miles an hour. My best idea for surviving the battle of the Beltway commute is the digestion of audiobooks, which has allowed me to consume numerous biographies and historical works, lots of literary art from Wendell Berry, and a good measure of science fiction (a hedonistic weakness since it is light on science but heavy on fiction). Between books I like to catch up on Radiolab (www.radiolab.org), a favorite podcast dealing with science topics from a human interest perspective.
A recent topic concerned CRISPR which stands for Clustered Regularly Interspaced Short Palindromic Repeats, a title even the most starched lab coated scientist would find boring. I preferred Radiolab’s description of CRISPR as “ninja-assassin-meets-DNA-editing-tool” which is cool and worthy of killing some driving time with.
For those readers, like myself, who have heard of CRISPR but really did not understand what all the fuss is about, indulge me for a brief (ridiculously oversimplified) description. Francisco Mojica, of the University of Alicante, Spain, was the first researcher to describe interesting bacterial genes with common repeating sequences and interspaced viral gene sequences in between. This confused scientists, who wondered why a bacterium genome would be harboring viral DNA? Dr. Mojica correctly theorized that this area of the bacterial genome represented an adaptive immune system against viral attackers. If you are a bacterium, viruses are Enemy No. 1. If a bacterium survived a viral attack it would store a small snippet of the viral DNA in its CRISPR region for later attacks. This allowed the bacterium to transcribe short RNA sequences (CRISPR RNAs) that contain a special protein (Cas9) to cut DNA and disrupt it. In a sense these CRISPR RNAs are like guided missiles that will seek out invading viral DNA, bind to it, and cleave it, thus destroying the attacking virus. Feng Zhang, a Broad Institute and Massachusetts Institute of Technology scientist, developed the first method to use the CRISPR-Cas9 system to cut DNA at specific spots and insert new DNA in the genome of mouse and human cells. In short, CRISPR is akin to the editing function of your word processing software allowing scientists to edit genetic information efficiently and inexpensively. Why should you care?
Scientists are already using this technology to tweak the human genome. To begin with, the mere fact that I am talking about humans “tweaking” the human genome should cause every healthcare provider a brief moment of incredulous thoughtful pause. On the one hand, some extremely powerful and exciting medicine is being accomplished with this technology. A Chinese group has been the first to modify a patient’s immune cells with CRISPR-Cas9 and inject them back into the patient to treat aggressive lung cancer.1 Many scientists see CRISPR as a revolutionary tool in the fight against cancer. For some time there has been concern about multiresistant strains of bacteria that no longer respond to antibiotic therapy, ushering in fears of a return to the preantibiotic era when infections were often fatal. Imagine taking a pill with CRISPR technology designed to seek out and destroy infecting bacterial DNA with precision heretofore unheard of. Consider the many genetic diseases such as Huntington’s disease or sickle-cell disease that may be corrected or rendered harmless with CRISPR. The potential for good in medicine seems boundless. Then there is the other hand.
There is a decidedly darker side to this technology. It is only a matter of time before CRISPR is used to genetically modify human embryos for decidedly less auspicious reasons (to my way of thinking) than curing disease. If you could pre-select the sex, hair or eye color, intelligence, height or any other attributes of your child, would you? Is this ethical? What consequences will this power have on the fabric of our society? If we could breed a better, more resilient, stronger and faster soldier to protect the country, should we? If we choose not to modify our military personnel, do we put ourselves at risk if other countries decide to do so? What about the potential for new and more deadly biological weapons? As this technology creeps into our food crops and animals, are there second- or third-order consequences of this manipulation? Are we prepared for these consequences?
These are just some of my questions, and I am not suggesting I have any of the answers. I am sure those of you reading this can think of many more consequences I have overlooked. I personally feel that CRISPR technology is a game-changer on par with language and the written word, the Industrial Revolution, and the computer chip. Mort Sahl’s comment about his life needing editing is at once both prophetic and horrifying when viewed through the lens of CRISPR. Fact, is dear reader, the gene-editing power of CRISPR is no longer the stuff of my juicy science fiction novel addiction; it is now part of the modern human condition and reality. We in federal medicine should not only be aware of this technology and its potential to revolutionize medicine, we better start thinking of some answers to the less-savory questions that CRISPR technology will soon demand answers.
1 http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988. Accessed 4 April 2017.