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Jul 31, 2015 | 09:04 GMT

9 mins read

Genetic Editing: Avoiding the GMO Controversy

Dr. Frank Thieme, manager of development at Icon Genetics, demonstrates the small-scale introduction of bacteria containing engineered DNA into Nicotiana benthamiana, a close relative of tobacco.
(SEAN GALLUP/Getty Images)
Forecast Bullets
  • As new technologies lead to reduced costs and improved accuracy, gene editing will become more prevalent.
  • Social debate and the inherent complexity of gene editing will delay applications in health care.
  • Gene editing will advance both industrial and agricultural biotechnology, but it is in the agricultural sector that gene editing will be most used in the near term.
  • The United States will remain a world leader in agricultural biotechnology, though China will likely become more competitive.

In geopolitics, we often take the wide-lens view, looking at the impersonal, sweeping factors that limit the influence of individuals. Yet the microscopic — genes and their manipulations — and the deeply personal still have the potential to affect the behaviors of nations in the years and decades to come. As gene-editing techniques continue to improve and new gene functions are uncovered, a wide swath of economic sectors will adjust to and incorporate these new discoveries. While health care implications may be the most obvious, they will not be the most immediate. Industrial biotechnology methods are likely to improve, but it is the agricultural industry that is poised to see the largest benefits from new gene-editing techniques.

As children, we find that some people can roll their tongues and others cannot. We learn that some pea plants are tall and others short, and that some traits are dominant over others. These simple rules of genetics, described by Gregor Mendel's laws, help explain the world we see, the phenotype. But genetics are far more complicated than the binary world that Mendel described back in the 1800s. The elucidation of the DNA double helix by Watson, Crick, Wilkins and Franklin in 1953 and the completion of the human genome project 50 years later are two major stepping stones on the path to understanding genes. However, the human race is still striving to fully comprehend the correlation between the microscopic (the genome) and the macroscopic (diseases and physical traits).

Brave New World

Though we may not have the whole picture, several diseases are associated with different genes or genetic mutations. In theory, and occasionally in practice, targeting and modifying these genes can result in a reversal of the disease. Genes in yeast, a simple test organism, were replaced in 1979, and the subsequent development of numerous techniques began in the 1980s. The idea is to exploit the cells' own repair mechanisms to fix cuts made at targeted locations — for instance, where a mutation occurs. Previously, techniques to do such editing were complicated and expensive; they were very specific to a given target because they relied on specific proteins, making widespread application more difficult. But advancements of a technique known as CRISPR-Cas9, which relies instead on RNA and a bacterial-derived single protein to target a site of interest in the genome, have made the application more widespread in recent years, significantly reducing the complexity and cost of the technique. Much like its predecessors, this editing technique uses an enzyme to cut at a specific location. Once this targeted section of DNA is cut, the existing DNA sequence can be changed or a new gene can be inserted. This relatively new gene editing technique has highlighted one of the more controversial aspects of gene editing in recent months.

A gene-editing technique known as CRISPR-Cas9,  like its predecessors, uses an enzyme to cut at a specific location. Once the targeted section of DNA is cut, the existing DNA sequence can be changed or a new gene inserted.

In April, Chinese scientists used CRISPR to edit a gene responsible for a blood disorder in embryos. The technique had previously been used in adult mice to reverse a liver disorder, but the trial in nonviable human embryos had poor to middling results, including off-target mutations when the CRISPR complex acted on other parts of the genome. The Chinese researchers may not have used the best technology available at the time, but as the technique continues to improve these off-target deletions will be significantly reduced. However, it also serves to illustrate that, although CRISPR technology is a significant advancement in the field, there is still room for development and improvement.

But even if success were assured, ethical questions would remain. There was public backlash resulting from the Chinese study, and some scientists are calling for a moratorium on gene editing until the risks of the new technique can be fully evaluated. However, because the technique is widely accessible and more broadly applicable than previous techniques, the ease of use likely will make complete oversight difficult.

Taking the idea of genomic editing to an extreme results in a "brave new world" of designer babies and super soldiers that would certainly give any country with the ability and willingness to harness the technology a geopolitical advantage. But neither the understanding of the human genome nor the scientific capability has reached the point where that is a reality and will not reach that point any time in the near future. Curing specific diseases, reducing the economic costs of endemic disease such as HIV and potentially extending the lifetimes of populations would be the first geopolitically relevant result of gene editing in medicine. Still, the complexity of the human genome and the ongoing ethical debate mean that any progress probably will be slower than developments in other sectors of the economy.

Skirting the GMO Label

But CRISPR and other techniques used to edit genes will not go unused as the ethical debate over human genomic editing continues. Rather, industry and agriculture will reap the benefits of cheaper, more accurate gene editing as CRISPR and other gene editing techniques continue to improve.

Industrial biotechnology uses living organisms like yeast, algae or bacteria to synthesize chemicals, plastics and fuels. Gene editing can be used to increase the efficiency of these processes and, in turn, possibly make the processes more cost competitive. Moreover, the need for such processes could grow as countries begin implementing policies in good-faith efforts to meet emission reduction targets.

In agriculture, the need to do more with less is more immediate. As the world's population increases, the middle class grows and drought and other extreme weather events are expected to become more prevalent in many areas, food demand is expected to rise in the coming years and decades. 

Farmers have been selectively breeding for desirable qualities long before the genes behind these qualities were identified. It was only when transgenic crops, in which a foreign gene is inserted into the plant's DNA, began to be used commercially in the 1990s that the term "genetically modified organism," or GMO, became part of the common lexicon on food. This first generation of genetic engineering, which focused on pest resistance and herbicide tolerance, is not the future of the industry. Genetic engineering is likely to focus on the assurance of more desirable traits, such as drought resistance and nitrogen uptake, and is not going away despite the social stigma associated with GMOs in some areas of the world. Advancements in biological techniques over the course of the last several years and a better understanding of various plant genomes have increased the ability to control these desired traits. Gene editing will be a necessary tool for future advancements in agricultural biotechnology and can save time over traditional crossbreeding methods. Mildew-resistant wheat and an herbicide-tolerant canola are just two examples in which gene editing is already being used.

Unlike the genetic modification that requires the insertion of a foreign gene, targeted mutagenesis using CRISPR or its protein-guided counterparts, Transcription activator-like effector nuclease or Zinc finger nuclease, relies on the cell to repair the cut to the double-stranded DNA made during the editing process. Gene-editing techniques can insert exogenous DNA, but they can also make the smaller changes to the genetic sequence by editing the genetic code as opposed to introducing an entirely new gene. The U.S. Department of Agriculture has already indicated through initial rulings that gene edits do not make an organism genetically modified if they do not contain transgenic sequences and are not generated using Agrobacterium (bacteria commonly used in GMOs to transfer genes into plants).

Because they would not be classified as GMOs, gene-edited plants would not be subject to the same time-consuming, rigorous approval process that genetically modified crops are and could reach the market much more quickly; they would reap the benefits of scientific advancements, without the stigma of a GMO label.

The U.S. Advantage in Agriculture

Without the GMO label, gene-edited crops are poised to enter the North American commercial market in the very near future: A gene-edited crop will enter the Canadian market in 2016. With a solid foundation in the academic world and a favorable entrepreneurial environment, the United States is set to remain a world leader in gene editing. The favorable rulings by the U.S. Department of Agriculture mean that gene-edited crops will be able to enter the market faster than their GMO counterparts.

The ambiguity in European legislation on gene-edited crops will likely delay commercialization in Europe because gene-edited crops are classified as GMOs in Europe, a traditionally hostile market. However, if the individual members of the European Union are given more freedom within the European Commission's rulings, similar to the recent changes in the GMO approval process, more GMO-friendly European nations such as Spain or the United Kingdom could enter the market for genetically edited crops. Even Germany, which at best can be considered neutral in the GMO debate, has classified gene-edited products under conventional breeding. This is not to say that the Europeans will not make strides in genomic editing at all. The industrial biotechnology sector in Europe is already well established, and with wider support to increase the environmental friendliness of many manufacturing processes, industrial biotechnology is likely to drive many of the advances toward further commercialization and advancement of gene-editing technology in Europe.

Additionally, China's burgeoning agricultural biotechnology sector will probably fully use the techniques. Chinese labs have already demonstrated less hesitation to attempt gene editing in human cells. Still, the United States will remain at the forefront of the movement. While there is still a dispute over which U.S. institution holds the patent for the powerful CRISPR technique — either the Broad Institute at Massachusetts Institute of Technology and Harvard or the University of California and its co-petitioners — the sheer number of patents related to the field will make it difficult for any single nation to supplant Washington as a world leader in agricultural biotechnology.

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