By George B. Kauffman
(Author’s note: This piece is based on Britt E. Erickson’s article, “Altering the Code of Life,” Chemical & Engineering News, June 29, 2015, Vol. 93, Issue 26, pp. 20–21).
The international Human Genome Project, the world’s largest collaborative biological project, which determined the sequence of chemical base pairs comprising human DNA (deoxyribonucleic acid) and identified and mapped all of the genes of the human genome from both a physical and functional standpoint, was completed in 2003, little more than a decade ago. DNA (deoxyribonucleic acid), the self-replicating material present in almost all living organisms as the main constituent of chromosomes and the carrier of genetic information, currently seems to be mentioned everywhere in TV, newspapers and all forms of media.
Now some researchers are trying to rewrite the human genome. Gene-editing technology provides relatively inexpensive, easy ways to delete, insert or replace genes in human cells to correct defects associated with diseases like cystic fibrosis and sickle cell anemia. Gene editing can also alter plant and animal genomes to boost agricultural yields and food production or modify insect genomes to reduce the spread of diseases like malaria. It is not only a tremendous scientific advance but is also potentially profitable commercially.
However, editing genes in human embryos, like many scientific advances, could have unintended consequences that are passed on for generations. It might be used to create designer babies with enhanced traits like high intelligence or greater beauty. Many scientists are also concerned that it could change the human germ line—the DNA in reproductive cells that is passed on from one generation to the next—in unexpected or dangerous ways.
In May, Chinese scientists reported that they had attempted to alter a gene associated with a potentially fatal blood disorder in the cells of nonviable human embryos (Protein & Cell, 2015, doi:10.1007/ s13238-015-0153-5). The experiment was unsuccessful. Most embryos died, or the gene targeted in the experiment was not altered. Even in several embryos where the gene was successfully modified, the scientists noted other DNA damage in their cells. Some scientists are worried that additional studies like it will soon follow.
Johns Hopkins University bioethics Professor Jeffrey P. Kahn suggested to lawmakers that scientific journals could serve as gatekeepers by not accepting papers related to research on gene editing unless authors provide details of an ethics review of the work. According to Kahn, the Chinese study “was reportedly rejected by both Science and Nature prior to its acceptance and eventual publication, with some reportage indicating that ethics reviews played a role in the decision to reject it.”
Earlier this year, before the Chinese scientists published their work, a group of leading scientists, bioethicists and law experts met in California, including several Nobel laureates, to map a plan to ensure that gene-editing technology is not used in a dangerous or unethical way.
They called for a moratorium on the use of gene-editing technologies for clinical application (Science, May 2015, doi:10.1126/science.aab1028). However, they did not say that research on editing genes in human embryos, eggs or sperm cells should cease.
Instead, they argued that the research on nonviable human embryos should continue if it does not result in pregnancies. The authors included University of California, Berkeley biochemist Jennifer Doudna, whose work on the immune systems of bacteria helped lead to the development of a widely used gene-editing technology called clustered regularly interspaced short palindromic repeats (CRISPR), which relies on the engineered CRISPR-associated protein 9 (Cas9). Although many scientists credit her for the invention, the first patents for the technology were granted to Feng Zhang, a scientist at the Broad Institute of the Massachusetts Institute of Technology. Both have established companies to commercialize the technology.
Doudna organized the California meeting when she began hearing rumors that scientists were using CRISPR-Cas9 to change DNA in human embryos. Chinese scientists had already used the technology to create genetically altered monkeys. A week before Doudna and 17 other scientists published their commentary in Science, a different group of scientists published a similar editorial in Nature (March 12, 2015, doi:10.1038/51March 12), seeking a moratorium on all gene editing of human embryos or human reproductive cells, including research in this area.
According to Edward Lanphier, president and chief executive officer of Sangamo BioSciences and a coauthor of the Nature editorial, “Genome editing in human embryos using current technologies could have unpredictable effects on future generations.” His group is developing new therapies for various diseases using a process that relies on zinc finger proteins—a rival technology to CRISPR-Cas9. Genetically engineering human germ-line cells is prohibited in many European countries, but not in the United States or China. However, federal research money cannot be used to fund such work in the United States.
According to National Institutes of Health Director Francis S. Collins, “The concept of altering the human germ line in embryos for clinical purposes has been debated over many years from many different perspectives and has been viewed almost universally as a line that should not be crossed. NIH will not fund any use of gene-editing technologies in human embryos.”
However, research supported by private funding in the United States is not subject to the same restrictions. There is little oversight unless the work attempts to establish a pregnancy, in which case researchers would require Food and Drug Administration (FDA) approval.
On June 16, Rep. Lamar Smith (R–Texas), chair of the House of Representatives Science, Space and Technology Committee, called the Chinese report “alarming” and stated “the U.S. can and should provide scientific and moral leadership” in this area (http://science. house.gov/press-release/subcommittee-examines-human-genetic-engineering). At the hearing, prominent scientists assured lawmakers that work is under way to better understand the ethical implications and risks of research involving gene-editing technology, especially when applied to human embryos.
National Academy of Medicine President Victor J. Dzau emphasized an initiative proposed in May by the National Academy of Sciences and the National Academy of Medicine to examine the risks and benefits of gene-editing research, including ethical considerations, and to generate a formal report to guide scientists, regulators and clinicians. He stated that an international meeting scheduled for this fall will examine ethical and governance issues at the global level.
Although most ethics concerns related to gene editing concern its use, some scientists have argued that “there may come a time when we would consider it unethical not to do editing of the germ line for certain kinds of applications,” such as treating serious diseases, Doudna stated. Gene-editing technology is widely available and is used in research applications. It will be several years before it is used in clinical applications in which cells are treated inside the body, she told the legislators. However, applications in which cells are modified, sequenced and validated outside the body and then reintroduced into the body are likely to be only one or two years away, she predicted.
Meanwhile, there is still a lot to be learned about “human genetics, gene-environment interactions, and pathways of disease,” she warned. “Would it be appropriate to use the technology to change a disease-causing genetic mutation to a sequence more typical among healthy people?” she asked. “Even this seemingly straightforward scenario raises serious concerns,” she said, “including the potential for unintended consequences of heritable germ-line modifications.”
George B. Kauffman, Ph.D., chemistry professor emeritus at Fresno State and a Guggenheim Fellow, is a recipient of the American Chemical Society’s George C. Pimentel Award in Chemical Education, the Helen M. Free Award for Public Outreach and the Award for Research at an Undergraduate Institution, as well as numerous domestic and international honors. In 2002 and 2011, he was appointed a Fellow of the American Association for the Advancement of Science and the American Chemical Society, respectively.