Regulators foil science's vitamin A deficit remedy

January 14, 2009Henry Miller

A group of multi-national European scientists has used gene-splicing techniques to create an extraordinary tomato.

It boasts a deep purple skin and flesh, and contains levels of antioxidants 200 percent higher than unmodified tomatoes. When fed to highly cancer-susceptible mice, the tomatoes significantly extended the mammal's lifespan.

These studies have received wide attention, but an equally momentous achievement of genetic modification has been largely ignored for almost a decade.

That innovation is Golden Rice, a collection of new rice varieties that is bio-fortified, or enriched, by genes that express beta-carotene, the precursor of vitamin A, which is converted in the body, as needed, to the active form.

Most physicians in North America and Europe never see a single case of vitamin A deficiency in their professional lifetimes.

But the situation is very different in poor countries, where vitamin A deficiency is epidemic among the poor, whose diet is heavily dominated by rice (which contains neither beta-carotene nor vitamin A) or other carbohydrate-rich, vitamin-poor sources of calories.

In developing countries, 200-300 million children of pre-school age are at risk of vitamin A deficiency, which can be devastating and even fatal.

It increases susceptibility to common childhood infections such as measles and diarrheal diseases, and is the single most important cause of childhood blindness in developing countries.

Every year, about 500,000 children become blind as a result of vitamin A deficiency, and 70 percent die within a year of losing their sight.

In theory, we could simply supplement children's diets with vitamin A in capsules, or add it to some staple foodstuff, the way that we add iodine to table salt to prevent hypothyroidism and goiter. Unfortunately, neither the resources - hundreds of millions of dollars annually °?°?- nor the infrastructure for distribution are available.

Biotechnology offers a better, cheaper, and more feasible solution: Golden Rice, which incorporates beta-carotene into the genetically altered rice grains.

The concept is simple. Although rice plants do not normally synthesize beta-carotene in the endosperm (seeds), they do make it in the green portions of the plant.

By using gene-splicing techniques to introduce the two genes that express these enzymes, the pathway is restored and the rice grains accumulate therapeutic amounts of beta-carotene.

Golden Rice offers the potential to make contributions to human health as monumental as the discovery and distribution of the Salk polio vaccine.

With wide use, it could save hundreds of thousands of lives every year and enhance the quality of life for millions more.

Bureaucratic dithering

But one aspect of this shining story is tarnished. Intransigent opposition by anti-science, anti-technology activists - Greenpeace, Friends of the Earth, and a few other groups - has spurred already risk-averse regulators to adopt an overly cautious approach that has stalled approvals.

There is nothing about Golden Rice that should require endless case-by-case reviews and bureaucratic dithering.

As the British journal Nature argued in 1992, a broad scientific consensus holds that "the same physical and biological laws govern the response of organisms modified by modern molecular and cellular methods and those produced by classical methods.... (Therefore) no conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes."

Put another way, government regulation of field research with plants should focus on the traits that may be related to risk - invasiveness, weediness, toxicity, and so forth - rather than on whether one or another technique of genetic manipulation was used.

Nine years after its creation, despite its vast potential to benefit humanity - and a negligible probability of harm to human health or the environment - Golden Rice remains hung up in regulatory red tape, with no end in sight. (Cancer-preventing tomatoes, take notice.)

By contrast, plants constructed with less precise techniques such as hybridization or mutagenesis generally are subject to no government scrutiny or requirements (or opposition from activists) at all.

That applies even to the numerous new plant varieties that have resulted from "wide crosses," hybridizations that move genes from one species or genus to another - across what used to be considered natural breeding boundaries.

Judith Rodin, the president of the Rockefeller Foundation, announced last October that her organization would provide funding to the International Rice Research Institute to shepherd Golden Rice through national regulatory approval processes in Bangladesh, India, Indonesia, and the Philippines.

This is good news, but what is really needed is a multi-faceted, aggressive reform of the regulatory process so that all new genetic constructions will have a chance to succeed.

In an April editorial in the journal Science, Nina Fedoroff, a plant geneticist who serves as senior scientific advisor to US Secretary of State Condoleezza Rice, wrote: "A new green revolution demands a global commitment to creating a modern agricultural infrastructure everywhere, adequate investment in training and modern laboratory facilities, and progress toward simplified regulatory approaches that are responsive to accumulating evidence of safety."

The Golden Rice story makes it clear that we do not yet have the will and the wisdom to make that happen.

The author is a physician and fellow at the Hoover Institution, and was an official at the US National Institutes of Health and at the Food and Drug Administration from 1977-1994. The views expressed are his own.