“Increased complexity” refers to a movement away from single-gene or single-pathway engineering using recombinant-DNA (rDNA) technology to the use of genome engineering to create multiplexed pathways and, at the extreme, engineered microbial communities for release in environments ranging from animal guts to large ecosystems. In considering biotechnology products, two biological “systems” are relevant: the host—the organism into which new material is introduced—and the source organism of the genetic material being introduced. Generally speaking, the majority of biotechnology products in commerce as of 2016—such as crops genetically engineered to resist herbicides or insects—were the result of the transformation of a well-characterized host organism, such as corn or soybean, with a few genes from another source organism that code for a desired trait, such as herbicide resistance along with a selectable marker gene to permit selection for transformed plants (Figure 2-6 [/books/NBK442203/figure/fig_2-6/?report=objectonly], column A). Such organisms are easily compared against their nontransformed (that is, nonbiotechnology) counterparts in risk assessments. As biotechnologies have matured over time, new types of products are being developed that allow for the transformation of less well-characterized hosts. For example, new genome-editing technologies allow developers to make changes in genomes of nearly any host organism for which there is a genome sequence available, from microbes to insects to mammals (Figure 2-6 [/books/NBK442203/figure/fig_2-6/?report=objectonly], columns B and C; Reardon, 2016). Advances in biotechnology also allow the introduction of novel, synthetic gene sequences and the creation of consortia—a collection of genes derived from multiple unrelated sources—which can be inserted into a host (Figure 2-6 [/books/NBK442203/figure/fig_2-6/?report=objectonly], column D). The products that fall in the second, third, and fourth columns are not as easily compared against a nontransformed (nonbiotechnology) counterpart. The challenge this presents to the regulatory system is discussed in Chapter 4 [/books/n/nap24605/ch4/].