Henry I. Miller

Common commodity crop plants such as corn and tobacco can now be programmed with gene-splicing techniques to produce high-value-added pharmaceuticals, a process dubbed “biopharming.” The plants are harvested, and the drug is then extracted and purified.

The concept is not new: For example, morphine and cocaine are derived from the opium poppy, and taxol and tetrahydrocannabinol come from the yew tree and marijuana plant, respectively. But biopharming’s great promise lies in the ability of gene-splicing techniques to make old plants do new things, and in the ingenious economy of the process: The energy for the manufacturing process comes from the sun, and its raw materials are water and carbon dioxide.

There are storm clouds on the horizon, however. The food industry fears that gene transfer or “volunteer” biopharmed plants in the field could contaminate the food supply with vaccines and drugs, triggering costly recalls and potential legal liability. Therefore, food producers are demanding stringent federal regulation—a quite literal example of NIMBY (Not In My Back Yard)-ism. However valid their desire to protect the food supply, their anxiety takes into account neither the realities of contemporary agriculture nor the nuances of biopharming.

Gene flow is ubiquitous. All crop plants have relatives somewhere, and some gene flow commonly occurs if the two populations are grown close together. Thus, genes could be transferred from a crop that has been modified to synthesize a pharmaceutical, but that phenomenon is likely to occur only if the gene confers a selective advantage to the recipient—an occurrence that should be uncommon with biopharming, because most often the added gene will make the plant less fit and able to proliferate.

Gene transfer is an age-old consideration for farmers, who have learned how to prevent pollen cross-contamination in the field when and if it is necessary for commercial reasons. For example, to maintain the highest level of genetic purity, distinct varieties of self-pollinated crops such as wheat, rice, soybean, and barley need to be separated by at least 60 feet, while certain insect-pollinated crops need wider segregation—a half-mile for watermelon and a mile for onion, for example.

However, human error is inevitable, as illustrated by the failure last year of Texas-based ProdiGene, Inc. to adequately monitor the test plots of biopharmed corn (synthesizing a vaccine to prevent Escherichia coli diarrhea in pigs) raised under contract by local growers in the Midwest. As a result, some 500,000 bushels of soybeans allegedly came into contact with a tiny amount of biopharmed corn stalks and leaves. The company was fined and the soybeans destroyed.

The ProdiGene case brings to mind the question, What is the likelihood of consumers sustaining injury, even in a worst-case scenario? The data necessary for a detailed analysis of the ProdiGene case are not publicly available, but for injury to occur, several highly improbable events would have to occur. First, the active drug substance would have to be present in the final food product—tofu, say, or salad dressing made with soybean oil—at sufficient levels to exert an adverse effect, the result of either direct toxicity or allergy. But there would have been a huge dilutional effect as the tiny amounts of biopharmed corn were pooled into the massive soybean harvest, and perhaps another dilution in the processed food. Second, the active agent would need to survive milling and other processing, and cooking. And third, it would need to be orally active.

The likelihood of all of these events occurring is extremely low. Moreover, the “drug” produced by the ProdiGene corn is not pharmacologically “active,” except in the sense that it is intended to elicit antibodies (that are intended to confer immunity to E.coli).

Before we redouble efforts to get regulators to impose debilitating restrictions on biopharmed plants and to enforce zero tolerances for contamination, we need to recall that grain-based products are highly prone to contamination—by highly toxic fungi, rodent droppings, and insect parts, for example. If regulators had set zero tolerances for these contaminants, the grain industry would be out of business. Instead, farmers, millers, and government have designed techniques for risk assessment and risk management, in order to handle, store, and process grain in a way that ensures consumer safety.

What’s grain for the goose should be grain for the gander. Instead of punishing biopharming to the point of oblivion, we need to reject the zero-tolerance, zero-risk mentality and approach safety scientifically and sensibly.

Henry I. Miller, M.D., former Director of the Food and Drug Administration’s Office of Biotechnology, is a Fellow at the Hoover Institution and the Competitive Enterprise Institute, Stanford University, Stanford, CA 94305-6010.