Regulation of Molecular Genetic Engineering Must Be Evidence-Based

By Henry I. Miller, MS, MD — Aug 17, 2023
For decades, excessive, unscientific regulation has slowed innovation using molecular genetic engineering. Policymakers must awaken to the realization that regulations based on pseudoscience or nescience are destructive and regressive. Tremendous innovations await, if only we have the wisdom to permit them to be developed.
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"Genetic Engineering" (GE) has been practiced by humans for more than 10,000 years, first by selecting and hybridizing plants. For almost half a century, newer molecular GE techniques have been used to modify plants, animals, bacteria and other organisms. Scientists can move desired genes virtually at will from one organism into another, or to alter genes with great precision but without introducing material from other organisms.

These kinds of genetic modifications have created significant breakthroughs in medicine, such as the production of blockbuster drugs and techniques for human gene therapy to treat cancer and genetic diseases. And in agriculture, the benefits include more nutritious food; disease-, pest- and drought-resistant plants; less use of chemical pesticides; and higher yields that conserve water and reduce the land needed for farming.

Although no unique risks or disadvantages of modern GE technology have been identified – quite the contrary, in fact — a few groups, especially anti-technology activists, have tried to discourage wider application instead promoting supposedly more "natural" processes and technologies.

In addition, governments have created new, costly regulatory regimens for the products of molecular GE in addition to the extensive regulatory frameworks that already existed for categories such as noxious weeds, toxins, and pesticides. The additional expense, prolonged reviews and delays in field testing have slowed scientific and pre-commercial advances and even resulted in the abandonment of promising innovations.

The question for boosting needed future food production is, can our planet really forego the best technologies in favor of biodynamic, regenerative, organic, or other "buzzword approaches" that incur increased costs, lower yields, and even greater risks to human health and the environment? Apparently, some consumers in developed countries have drunk the activists' Kool-Aid and think so. Richer countries can absorb the impacts of unwise decisions, but when misguided, regressive views are adopted by developing nations where food production is a larger, more critical part of the economy, the result can be debilitating or even catastrophic. Two recent examples are Sri Lanka and Mexico, discussed below.

First, let us try to make sense of what the various labels applied to agricultural production mean. Organic originally meant "locally grown." Only later did this terminology evolve to mean that no pesticides or other agricultural chemicals would be used. A prevalent "green myth" about organic agriculture is that it does not employ pesticides. Organic farming does, in fact, use some chemicals to prevent predation of its crops. More than 20 are commonly used in the growing and processing of organic crops and are acceptable under the U.S. Department of Agriculture's arbitrary and ever-shifting organic rules. Many of those organic chemicals are extremely toxic and are known carcinogens. Consider, for example, copper sulfate and other cupric compounds, which are banned in most European countries for organic grape production. In the U.S., however, they are approved for organic grape production because powdery mildew is devastating in North America (but not in Europe).

Moreover, often overlooked is that 99.99% of the pesticidal substances in our diet comes from plants that produce them naturally (1) to defend themselves from predators.

Over the centuries, the main culprits in mass food poisoning have often been mycotoxins, such as aflatoxin from Aspergillus, ergotamine from ergot, or fumonisin from Fusarium species. Mycotoxins come from fungal contamination of unprocessed crops, or when insects attack food crops and open plant wounds that might provide an opportunity for pathogen invasion. Once the molds get a foothold, poor storage conditions also promote their post-harvest growth on grain.

Aflatoxin is globally the most prevalent mycotoxin, as well as being characterized by extreme toxicity which is additive over time. That means that exposures are cumulative. Organic or other, so-called "natural" types of agriculture have few proven anti-fungal treatments. Peanut production in most locations has strong recommendations to treat seed for planting with fungicides, but organic production doesn't allow it. As with other mycotoxins, organic foods often have several-fold higher concentrations of aflatoxin than food from traditional agricultural production that permits a wide choice of fungicide treatments.

Exhaustive studies that compared production methods, such as those described in a landmark report published by the National Academy of Sciences, Engineering and Medicine (2), have failed to show measurable health benefits or lower risks from the more "natural," trendy approaches. Therefore, proponents of the latter have had to resort to extolling mystic or spiritual improvements as the rationale for using them. Perhaps the biodynamic concept of burying cattle horns packed with manure according to seasonal changes is in fact an improvement, but we don't have evidence to substantiate these claims. Thus, in the end we are supposed to believe it's better as an article of faith.

The fatal flaw of organic agriculture is the low yields that cause it to be wasteful of water and farmland. Plant pathologist Steven Savage of the CropLife Foundation analyzed the data from the USDA's 2014 Organic Survey (3), which reported various measures of productivity from most of the certified organic farms in the nation, and compared them to those at conventional farms. His findings were extraordinary. In 59 of the 68 crops surveyed, there was a yield gap, which means that, controlling for other variables, organic farms were producing less than conventional farms. Many of those shortfalls were large: For strawberries, organic farms produced 61 percent less than conventional farms; for tangerines, 58 percent less; for cotton, 45 percent less; and for rice, 39 percent less.

As Savage observed: "To have raised all U.S. crops as organic in 2014 would have required farming of 109 million more acres of land. That is an area equivalent to all the parkland and wildland areas in the lower 48 states, or 1.8 times as much as all the urban land in the nation."

The U.S. Department of Agriculture is in the awkward position of overseeing "organic" standards while harboring no illusions about what the designation means. "Let me be clear about one thing," U.S. Secretary of Agriculture Dan Glickman said (4) when organic certification was created. "The organic label is a marketing tool. It is not a statement about food safety. Nor is 'organic' a value judgment about nutrition or quality." Yet USDA's own research shows that consumers buy higher priced organic products because they mistakenly believe them to be safer and/or more nutritious.

Government regulation further complicates the landscape. "Organic" agriculture bans plants modified with molecular techniques although GE is a seamless continuum of techniques that have been used over millennia. These include (among others) hybridization, mutagenesis, somaclonal variation, wide-cross hybridization (movement of genes across "natural breeding barriers"), recombinant DNA ("gene splicing"), and now gene-editing (5). The primary distinction between the last two and the others is they are far more precise and predictable than the earlier techniques, which often introduce off-target mutations.

Since the advent in the 1970s of recombinant DNA technology, which enables segments of DNA to be moved readily and more precisely from one organism to another, molecular GE techniques have become ever more sophisticated, precise, and predictable. This evolution has now culminated in the most recent discoveries, the CRISPR-Cas9 system and its variations. This technology can find a specific sequence of DNA (6) inside a cell and then precisely alter it. CRISPR can also be used to turn genes on or off without altering their sequence.

An article (7) published in April 2023 by a group of German researchers illustrates how regulatory approaches can become mired in bio-babble when they forsake the fundamentals of science – specifically, when they ignore that there exists a seamless continuum between old and new techniques for genetic modification. Instead, they got caught up in meaningless distinctions and labels, such as "new genomic techniques" (NGTs) and "genetically modified organisms" (GMOs), and then proposed arbitrary, nonsensical approaches to regulating them. This summary of the paper is illustrative (emphasis added):

New genomic techniques (NGTs) allow new genotypes and traits to be developed in different ways and with different outcomes compared to previous GE methods or conventional breeding (including non-targeted mutagenesis). EU GMO regulation requires an assessment of their direct and indirect effects that may be immediate, delayed or cumulative. Such effects may also result from the interactions of NGT organisms simultaneously present in a shared receiving environment or emerge from a combination of their traits. This review elaborates such potential interactions based on a literature review and reasoned scenarios to identify possible pathways to harm.

Main findings: NGT organisms might be introduced into the environment and food chains on a large-scale, involving many traits, across a broad range of species and within short periods of time. Unavoidably, this would increase the likelihood that direct or indirect effects will occur through interactions between NGT organisms that are, for example simultaneously present within a shared environment. It has to be assumed that the cumulative effects of these NGT organisms may exceed the sum of risks identified in the distinct 'events'. Consequently, risk assessors and risk managers not only need to consider the risks associated with individual NGT organisms ('events'), but should also take account of risks resulting from their potential interactions and combinatorial effects. In addition, a prospective technology assessment could help the risk manager in defining criteria to minimize potential unintended interactions between NGT organisms through limiting the scale of releases.

Conclusions: If genetically engineered (GE) organisms derived from NGTs are released into the environment, their potentially negative impacts need to be minimized. In addition, the introduction [of] prospective technology assessment could provide an instrument for the risk manager to control the scale of releases of NGT organisms.

By ignoring the seamless continuum of techniques for genetic modification referred to above, the authors' logic dictates that every time a new cultivar or variant — such as Nobelist Norman Borlaug's dwarf wheat varieties, colchicine-induced triploidy (meaning three sets of chromosomes) which give us the banana fruit without a mouthful of large seeds, the mutant peach we call a nectarine, the tangerine-pomelo hybrid called a tangelo, or recombinant DNA-modified, pest-resistant Bt-corn, etc., etc. — is introduced, there would need to be risk-assessments to consider not only "direct and indirect effects that may be immediate, delayed or cumulative" but "should also take account of risks resulting from their potential interactions and combinatorial effects" with other "organisms that are, for example simultaneously present within a shared environment."

In other words, the risk analysis of every field trial of a new variant would need to consider its possible interaction with every extant organism, from bacteria and viruses to trees, migratory birds, and animals, including humans. In mathematical terms, one would have to consider the possible risks of N factors taken one to N at a time. This illustrates the absurdity of the European "precautionary principle" – that anything and everything is dangerous until proven otherwise – taken to its extreme. It illustrates how you end up in logical La La Land when you get the basic assumptions wrong.

If such bureaucratic bumbling spills over into developing countries, it can lead to destruction of economies, and even to food insecurity and political instability. The catastrophic example of Sri Lanka is a recent, real-life example of the misery that can result from the abandonment of science and common sense. With the imposition of the new "Green Sri Lanka" policy imposed on the nation in 2021, the country converted completely to organic agriculture and banned the importation of synthetic fertilizers and other chemical inputs, including pesticides and herbicides. As a result, agricultural production plummeted and rural poverty soared. The result was damage to the economy and widespread famine and riots that led to the president fleeing the country – the result of uninformed, flawed policy based on wishful thinking instead of science.

Mexico has been on the verge of similar, albeit less sweeping, policies. A presidential decree (8) on "GM corn" in 2020 bans it in dough or tortillas, jeopardizing Mexico's demand for corn imports. The country later modified its decree (9), eliminating the deadline to ban GM corn for animal feed and industrial use, which is by far the bulk of its U.S. corn imports. This would be devastating for American corn producers and Mexican consumers alike. Mexico bought more than 20 million metric tons of corn from the United States in the 2021-22 marketing year, which runs from September to August, according to the U.S. Department of Agriculture, and there is no way that Mexican farmers would be able to make up the shortfall.

Science must prevail. Policymakers worldwide should heed the unfortunate examples of Sri Lanka and Mexico, and realize that regulations based on pseudoscience or nescience are destructive and regressive. Tremendous innovations are waiting, if only we have the wisdom to permit them to be developed.

An earlier version of this article was published previously by European Scientist.










Henry I. Miller, a physician and molecular biologist, is the Glenn Swogger distinguished fellow at the American Council on Science and Health. He was the founding director of the FDA's Office of Biotechnology. David W. Altman, PhD, MBA, is a geneticist and long-time academic. He is currently President of IPR Consulting, Inc.

Henry I. Miller, MS, MD

Henry I. Miller, MS, MD, is the Glenn Swogger Distinguished Fellow at the American Council on Science and Health. His research focuses on public policy toward science, technology, and medicine, encompassing a number of areas, including pharmaceutical development, genetic engineering, models for regulatory reform, precision medicine, and the emergence of new viral diseases. Dr. Miller served for fifteen years at the US Food and Drug Administration (FDA) in a number of posts, including as the founding director of the Office of Biotechnology.

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