The debate over precision genome engineering (column)
A debate has emerged in the scientific world concerning genome engineering. Recently, there have been amazing advances in scientists’ ability to modify genetic material. It is now possible to manipulate the human genome with extreme precision using new engineering techniques. Individual genes can be removed and replaced with a different version, or specific mutations can be corrected, while avoiding damage to unrelated parts of the genome. The technique has opened up opportunities for gene therapies to repair malfunctioning genes and control infectious agents such as the human immunodeficiency virus that causes AIDS. But it can also be applied to human embryos, opening up the potential of correcting mutated genes that cause inherited diseases by changing an embryo’s DNA before implantation in the womb. At the same time, it could be used by fertility doctors to add desirable traits to the embryo, producing “designer babies.” Not surprisingly, these advances have raised alarms among scientists, bioethicists and the public at large.
Simpler technologies to manipulate genetic material have been around for many years. DNA is comprised of long strands of molecules called nucleotides that come in four flavors: A, T, G and C. Traditional genetic engineering approaches involve cutting and pasting these strands to create new sequences. The basic approach involves so-called “restriction enzymes” that are able to recognize specific sequences and cut the DNA at that point. For example, the enzyme EcoR1 cuts DNA at the sequence “GAATTC.” Other enzymes can paste DNA fragments back together. Restriction enzymes come in many types with many different sequence specificities and have been a mainstay of genetic engineering for decades. However, these enzymes lack the precision to engineer the human genome because they interact with sequences of only 1 to 10 nucleotides that occur more or less randomly throughout the genome.
In recent years, several advances in our ability to manipulate and engineer DNA have revolutionized the field. These new approaches involve the creation of artificial restriction enzymes engineered to cut DNA at any desired sequence. One such technology, referred to as CRISPRs, takes advantage of a mechanism that bacteria use to protect themselves against viruses. Bacteria produce structures (CRISPRs) able to kill invading viruses by capturing sequences of genetic material from the virus and using them as a template to recognize and cut viral genetic material. The damage to the viral genetic material prevents the virus from replicating and thereby protects the bacterium. Scientists have commandeered this mechanism by introducing synthetic sequences of genetic material that direct the cutting of DNA at a desired sequence. The ability to control the sequence to be cut allows genetic engineers to manipulate DNA with a precision previously unimaginable and with the potential for both good and evil purposes.
The debate erupted into public view after 18 leading scientists wrote an open letter calling for regulation of this technology. The letter, entitled “A prudent path forward for genomic engineering and germline gene modification” discusses “the scientific, medical, legal and ethical implications of these new prospects for genome biology.” The authors specifically want to discourage the technology’s use for engineering human germline cells to generate human embryos. Their central concerns are for “unknown risks to human health and well-being.” Obviously, such studies pose important ethical questions, so there needs to be a thorough airing of the ethics involved.
Let’s hope the scientific community can come to a sensible consensus on the use of this powerful technology. The matter has become even more urgent with two recent developments. First, researchers have now modified CRISPRs such that they are able to turn genes on and off. In this case, CRISPRs are targeted directly to the genes’ on/off switch. Second, researchers have re-engineered the CRISPR mechanism four-fold smaller so it can more easily enter cells. This makes the technology more usable as a drug to treat certain genetic diseases. And third, the CRISP mechanism has been modified to target RNA molecules that translate messages from the DNA into proteins, enabling researchers to modify protein production in the cell. These exciting advances are occurring at breakneck speed and will require constant vigilance by all of us.
David L. “Woody” Woodland, Ph.D. is the chief scientific officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at 970-262-1230 ext. 131 or firstname.lastname@example.org.
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