The road to the farm is bumpy

Regulations misled by perception

The 1980s saw the development of the technologies required to introduce (transform) and express genes in plants. Transformation and regeneration of monocots (i.e. the group of plants that includes cereals, grasses, lilies, or orchids) was harder to attain than that of their dicot counterparts, and were achieved only by the end of the decade. This was the area of expertise of Prof Ingo Potrykus, who was a professor at the Swiss Federal Institute of Technology in Zurich.

Most of the science required to engineer the carotenoid pathway in the rice (a monocot) grain was developed in the 1990s. This is the area of expertise of Prof Peter Beyer, where he has notably contributed to a better understanding of the underlying biochemical mechanisms involved.

The breakthrough achievement of 1999 showed that it was possible to reconstitute the carotenoid pathway —which is naturally active in leaves but not in the grain— in rice grains, something even many experts did not believe was possible. After the proof of concept was achieved, the project entered into the development phase. One of the less pleasant tasks that comes with product development is to obtain regulatory approval, which is required by every country for the release of genetically modified plants into the environment. This is a mandatory step, which at present is overly lengthy and costly—it can cost several million dollars because of the extensive toxicity and allergenicity testing involved, comparable to those applicable to a pharmaceutical product and not applied to plant variants produced in many other different ways

Access to Intellectual Property Rights (IPR) —which many thought would constitute the main barrier to the dissemination of Golden Rice— was achieved in 2000. The process took less than six months of negotiations. The deal involved the creation of a private-public partnership between the inventors and the agrichemicals company Syngenta. This partnership facilitated the access to a number of key technologies held by multiple players in the field of biotechnology. The required material transfer agreements (MTAs) were signed in 2001.

The next necessary step consisted in identifying a partner capable of producing hundreds of transgenic rice lines from which regulatory clean events could be identified. The term regulatory clean refers to individual transformants (plants derived from one singly genetically modified cell) capable of complying with the multitude of regulatory requirements. Every single event requires a separate approval process.

It was shown early in the process that the provitamin A-production trait was transferable to any rice variety, including the indica type, widely grown in southeast Asia, where vitamin A deficiency is rampant. But these varieties are also technically the most difficult to transform. Once a useful transformation event has been obtained in a rice variety belonging to any of the cultivated varietal groups (japonica, indica, javanica), the trait can be transferred from one variety to the other by conventional breeding techniques. Alternatively, the necessary genes can be introduced directly by genetic transformation. The latter is the less preferred option, at least as long as the regulatory approval procedures remain as demanding as they are at present, i.e. the whole regulatory package must be produced for each transformation event, even if the same genes are introduced.

The first regulatory clean event was obtained in 2002, and a regulatory clean line with a β-carotene content of 1.6 µg/g was obtained in 2003.

2004 – Golden Rice meets the sun in the open

The first Golden Rice field trial in the world was harvested in September 2004 in Crowley ("where life is rice and easy"), Louisiana, USA. It may sound surprising to many that five years went by before Golden Rice could be planted in an open field. A main reason for this delay was that target countries for Golden Rice —i.e. those with high rice consumtpion and a high vitamin A deficit— did not have biosafety regulations in place at the time. A necessary condition attached to the agreement with Golden Rice licensees is that no field releases may take place in the absence of a national regulatory framework. The delay shows how complicated life has become for developing countries. Even in the face of human misery, that could be alleviated with the help of a transgenic plant, developing countries are still struggling with multiple pressures that make access to the technology almost impossible.

The reason the first field trial was carried out in collaboration with Louisiana State University, is that the USA is one of the few countries in the world where field trials with transgenic plants can be carried out after complying with an acceptable, well-defined set of regulatory requirements.

In the field, the transgenic Golden Rice plants were indistinguishable from their parent variety, while β-carotene accumulation was higher than for parental materials grown in the greenhouse. While β-carotene in first generation Golden Rice was not high enough to cover the recommended daily requirements of people with acute vitamin A deficiency, the experiment showed that, in the field, grains accumulated about four times more β-carotene than in the greenhouse, possibly due to better growth conditions. An average of 6 μg/g β-carotene was obtained for the grains from the 2004 field trial. The same year, new experimental lines (GR2) with more than six times as much β-carotene were obtained in the greenhouse!, which is 23 times more than in the prototype Golden Rice obtained in 1999.

A happy day finally saw Ingo Potrykus and Peter Beyer watching over the first Golden Rice field trial in the world in Crowley, Louisiana, in September 2004. Many years of steady work and perseverance in the face of many sceptics had finally paid out.

A recount of the Golden Rice story by Ingo Potrykus can be found at "The Golden Rice Tale".