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Date:

March 17, 2001

Subject:

Ingo Potrykus: Golden Rice and Beyond

 

http://www.plantphysiol.org/cgi/content/full/125/3/1157?maxtoshow=&HITS=&hits=&RESULTFORMAT=&fulltext=ingo&searchid=QID_NOT_SET&stored_search=&FIRSTINDEX=&volume=125&issue=3#B6

Plant Physiology, March 2001, Vol. 125, pp. 1157-1161
http://www.plantphysiol.org/current.shtml

EDITOR'S CHOICE

Golden Rice and Beyond

Plant Physiology
By Ingo Potrykus
March 2001

INTRODUCTION

Professor Emeritus, ETH Zurich, Switzerland; Member of Academia Europaea;
and Recipient of the International Society for Plant Molecular Biology
2000 Kumho Science International Award


EMOTIONS ARE THE PROBLEM, NOT RATIONAL DISCOURSE

The term "golden rice" was coined by a Thai businessman who is active in
initiatives aimed at reducing the birth rate, a major cause of the food
security problem. As it turned out, the term "golden rice" has proven to
be enormously successful in piquing the interest of the public. (I gave up
tallying its mention in the popular media after more than 30 television
broadcasts and 300 newspaper articles, but I am still busy with requests
for interviews every week.) It is difficult to estimate how much of its
celebrity stems from its catchy moniker and how much is from the
technological breakthrough it represents. Needless to say, we live in a
society that is strongly influenced (not to say manipulated) by the media.
As the popular media live by selling news, "catchy" names are especially
useful in attracting the interest of media consumers. The "story,"
however, must also be accompanied by an important message, in this case,
that the purely altruistic use of genetic engineering technology has
potentially solved an urgent and previously intractable health problem for
the poor of the developing world. And this is my first message and my
response to Chris Somerville's (2000) contribution: I, too, believe in the
power of education and rational discourse. However, after more then 10
years on the frontlines of the public debate concerning genetically
modified organisms (GMOs), I have learned that even with the help of the
media, rational arguments succeed in influencing only a small minority of
the public-at-large. In short, rational arguments are poor ammunition
against the emotional appeals of the opposition. The GMO opposition,
especially in Europe, has been extraordinarily successful in channeling
all negative emotions associated with the supposed dangers of all new
technologies as well as economic "globalization" onto the alleged hazards
presented by the release of GMOs into the food chain. This is one reason
why the story of "golden rice" is so important: In the short history of
GMO research, "golden rice" is unique in having been embraced by the
public-at-large. The reason for this, I believe, lies in its emotional
appeal: People are truly concerned about the fate of blind children, and
they are willing to support a technology that offers the children at risk
the opportunity to avoid blindness.

I fully agree with the opinion of Maarten Chrispeels (2000) that "food
security" for developing countries is one of the major challenges for
mankind. I believe that scientists, as a privileged group of citizens,
have more than an academic responsibility to advance science: They must
also accept a higher social responsibility and, wherever possible, use
science to help solve the important problems not of industry, but of
humanity. In this respect our scientific community is not in balance, and
the public senses this intuitively. This, in turn, has made it easy for
the GMO opposition to wage a war of propaganda against our work with
arguments to the effect that we are only pretending to work for mankind,
or are only satisfying our own egos, or are working merely for the profits
of industry. For example, laypeople often ask if food security for
developing countries is such a dire problem, and if scientists feel that
GMO technology should be developed to contribute to a solution, then why
are so many scientists working on Arabidopsis and so few on those plants
that feed the poor? Of course, one can pontificate about the importance of
basic research and how all the knowledge gained from Arabidopsis will
ultimately expedite the improvement of major crops, but one realizes that
the average citizen remains emotionally unswayed by such arguments. The
public's skepticism is heightened by the fact that many scientists do have
funds from industry and, therefore, have their sensiblities attuned to
solutions of problems of interest to industry. Press releases from the
agrobiotechnology industry relating to work on food security in developing
countries are taken as disingenuous and serve only to foster ill will
against the technology. So what can we do to improve the public sentiment
about the technology? We need more examples of the "golden rice" type;
namely, successful projects that were developed in public institutions
using public funding that address an urgent need, are not solvable with
traditional techniques, are being made available free of charge and
limitations to the poor, and have no deleterious effects on the
environment or human health.


GOLDEN RICE: THE SCIENTIFIC CHALLENGE

In the early 1990s, when we proposed to the Rockefeller Biotechnology
Program (New York) to initiate a project to genetically engineer the
provitamin-A pathway into the rice endosperm, we were fortunate that the
Rockefeller Foundation had already had similar thoughts. The Foundation
responded readily by organizing a brainstorming session. The verdict of
this initial session was that such a project had a low probability of
success, but that it was worth trying because of its high potential
benefit. That is how Peter Beyer (University of Freiburg, Germany) and I
got together, and this collaboration turned out to represent an ideal
combination of skills. Peter Beyer was studying the regulation of the
terpenoid pathway in daffodil and was working on the isolation of those
genes we would need to establish the pathway in rice endosperm, whereas I
had the engineering technology and was nave enough to believe that the
project was feasible. Navet was an important component because all those
with appropriate knowledge had cited numerous reasons for skepticism. Our
research determined that the last precursor of the pathway in endosperm
was geranlygeranyl-pyrro-phosphate and, as a consequence, it theoretically
should be possible to reach -carotene via four enzymes: phytoene synthase,
phytoene desaturase, -carotene desaturase, and lycopene cyclase (Burkhardt
et al., 1997). There were hundreds of scientific reasons why the
introduction and coordinated function of these enzymes would not be
expected to work. Those with the necessary scientific knowledge were right
in not believing in the experiment. When we finally had "golden rice" I
learned that even my partner, Peter Beyer, and the scientific advisory
board of The Rockefeller Foundation, except for Ralph Quatrano, had not
believed that it could work. This exemplifies the advantage of my
ignorance and navet: With my simple engineering mind I was optimistic
throughout and therefore carried the project through, even when
Rockefeller stopped funding Peter Beyer's group. Altogether it took 8
years, but the first breakthrough came when Peter Burkhardt of my
laboratory recovered phenotypically normal, fertile, phytoene
synthase-transgenic rice plants, which produced good quantities of
phytoene in their endosperm (Burkhardt et al., 1997). This demonstrated
two important facts: It was possible to specifically divert the pathway
toward -carotene, and channeling a considerable amount of
geranlygeranyl-pyrrophosphate away from the other important pathways had
no severe consequences on the physiology and development. Xudong Ye of my
laboratory did the crucial experiment: cotransformation with two
Agrobacterium strains containing all the necessary genes plus a selectable
marker. The resulting yellow-colored endosperm contained provitamin A and
other terpenoids of nutritional importance and to everybody's surprise
demonstrated that it was possible to engineer the entire biochemical
pathway (Ye et al., 2000). A further key figure in our research was Salim
Al-Babili from Peter Beyer's group who supplied all the successful
constructs. The highest provitamin-A-producing line contains enough
provitamin A (1.6 g g1 endosperm) to expect a positive effect in
relieving vitamin-A deficiency, but of course this has to be tested with
bioavailability and feeding studies. However, these cannot be performed
with the few grams of rice we can produce in our containment greenhouse.
This will require hundreds of kilograms, which can be produced only in the
field, and field release is still a problem in Europe, as it is in
developing countries. (We are faced with a strong political movement for a
10-year moratorium in Switzerland.)


GOLDEN RICE: THE CHALLENGE OF INTELLECTUAL PROPERTY RIGHTS (IPRs)

"Golden rice" was developed to prevent vitamin-A deficiency in the poor
and disadvantaged of developing countries. To fulfill this goal it has to
reach the subsistence farmers free of charge and restrictions. Peter Beyer
had written up a patent application, and Peter and I were determined to
make the technology freely available. Because only public funding was
involved, this was not considered too difficult. The Rockefeller
Foundation had the same concept and the Swiss Federal Institute of
Technology (Zurich) supported it, but the European Commission had a clause
in its financial support to Peter Beyer, stating that industrial partners
of the "Carotene Plus" project, of which our rice project was a small
part, would have rights to project results. (The framework [IV and V] of
European Union [EU] funding forces public research into coalitions with
industry and thus is responsible for two very questionable consequences:
Public research is oriented toward problems of interest to industry, and
public research is losing its independence.) We did not consider this to
be too big a problem because the EU funding was only a small contribution
at the end of the project, but we soon realized that the task of
technology transfer to developing countries, the international patent
application, and the numerous IPRs and technical property rigths (TPRs) we
had used in our experiments were too much for two private persons to
handle properly. We urgently needed a powerful partner (because of the
deadline of the international patent application). In discussions with
industry the definitions of "subsistence farmer" and "humanitarian use"
were the most difficult problems to be solved. We wanted a definition as
generous as possible, because we not only wanted the technology to be free
for small-scale farmers, but we also wanted to contribute to poverty
alleviation via local commercial development. It is very fortunate that
the company that agreed to the most generous definition was also the
company that had legal rights because of its involvement in the EU
project. This facilitated the agreement, via a small licensing company
(Greenovation, Freiburg, Germany), with Zeneca (Fernhurst, UK). Zeneca
received an exclusive license for commercial use and in return supports
the humanitarian use via the inventors for developing countries. The
cutoff line between humanitarian and commercial use is $10,000 (income
from "golden rice"). This agreement also applies for all subsequent
applications of this technology to other crop plants. It turned out that
our agreement with Zeneca and the involvement of our partner in Zeneca,
Adrian Dubock, were real assets in developing the humanitarian aspect of
the project. Adrian was very helpful in reducing the frightening number of
IPRs and TPRs. He also organized most of the free licenses for the
relevant IPRs and TPRs such that we are now in the position of granting
"freedom to operate" to those public research institutions in developing
countries to proceed in introducing the trait into local varieties.
Publicity sometimes can be helpful: Only a few days after the cover story
about "golden rice" had appeared in Time, I had a phone call from Monsanto
offering free licenses for the company's IPR involved.


MAKING BEST USE OF (NOT FIGHTING ABOUT) PATENTS HELPS THE POOR AND
UNDERPRIVILEGED

At this point it is appropriate to add a more general comment on patents
and the heavy opposition against patenting in life sciences. Because we
did not know how many and which IPRs we had used in developing the "golden
rice," and because further development for the humanitarian purpose
required "freedom to operate" for the institutions involved, The
Rockefeller Foundation commissioned an IPR audit through the International
Service for the Acquisition of Agri-Biotech Applications. The outcome was
shocking (International Service for the Acquisition of Agri-Biotech
Applications brief nos. 20-2,000). There were 70 IPRs and TPRs belonging
to 32 different companies and universities, which we had used in our
experiments and for which we would need free licenses to be able to
establish a "freedom to operate" situation for our partners, who were keen
to begin further variety development. Because I was also blocked by an
unfair use of a material transfer agreement, which had no causal relation
to "golden rice" development, I was initially upset. It seemed to me
unacceptable, even immoral, that an achievement based on research in a
public institution and exclusively with public funding and designed for a
humanitarian purpose was in the hands of those who had patented enabling
technology earlier or who had sneaked in a material transfer agreement in
the context of an earlier experiment. It turned out that whatever public
research one was doing, it was all in the hands of industry (and some
universities). At that time I was much tempted to join those who fight
patenting. Upon further reflection, however, I realized that the
development of "golden rice" was only possible because of the existence of
patents. Much of the technology that I had been using was publicly
available only because the inventors, by patenting, could protect their
rights. Without patents, much of this technology would have remained
secret. To take full advantage of available knowledge to benefit the poor,
it does not make sense to fight against patenting. It makes far more sense
to fight for a sensible use of IPRs. Thanks to public pressure there is
much goodwill in the leading companies to come to an agreement on the use
of IPR/TPR for humanitarian use that does not interfere with commercial
interests of the companies. An interesting discussion of this issue was
part of a recent satellite meeting associated with the World Food Prize
Symposium 2000 in Des Moines, Iowa (for more information, contact C.S.
Prakash, e-mail: prakash@acd.tusk.edu).

We are now in a situation in which we have verbal confirmation for free
licenses for humanitarian use for all intellectual and technical property
involved. To date, details cannot yet be disclosed because some IPR owners
prefer anonymity. Thanks to the interest of the agbiotech companies to use
"golden rice" for better acceptance of the GMO technology, and thanks to
the pressure against GMOs built up by the opposition, the IPR situation
was easier to solve than expected.


GOLDEN RICE: THE CHALLENGE OF TECHNOLOGY TRANSFER

Having overcome the scientific problems, and having achieved freedom to
operate, leaves technology transfer as the next hurdle. This is a far
bigger task that anyone having no personal experience should assume.
"Golden rice" so far consists of a series of provitamin-A-producing
laboratory lines (TP 309). The characters of these lines must be
transferred to as many locally adapted varieties and ecotypes in as many
rice-growing countries as quickly as possible, and this transfer has to be
organized such that all rules and regulations concerning the handling and
use of GMOs will be strictly followed. Although we have had requests from
many institutions in many countries, we believed it would be unwise to
start the technology transfer on too large a scale. To aid in this
endeavor, we have established a "Golden Rice Humanitarian Board" to help
make the right decisions and to provide secretarial support. Again, our
decision to work with Zeneca was extremely helpful. Adrian Dubock was
willing to care for the task of the secretary. We have additional
invaluable help from Katharina Jenny from the Indo-Swiss Collaboration in
Biotechnology (ETH Zurich), an institution jointly financed by the Indian
Department of Biotechnology (DBT; New Delhi, India) and the Swiss
Development Corporation (Bern, Switzerland). Golden rice will be
introduced into India in the established organizational framework of the
Indo-Swiss Collaboration in Biotechnology, which has 10 years of
experience in technology transfer. Thanks to this situation and thanks to
the strong commitment of the DBT and the Indian Council for Agricultural
Research (New Delhi, India), India will take a leading role and can serve
as a model for other countries. The project will begin with a careful
assessment of needs, an analysis and comparisons of the pros and cons of
alternative measures, and setting a framework for the optimal and
complementary use of "golden rice." Of course, there will be
bioavailability, substantial equivalence, toxicology, and allergenicity
assessments and we are grateful for offers from specialists to help.
Careful socioeconomic and environmental impact studies will help to avoid
any possible risk and make sure that the technology reaches the poor. Care
will be taken that the material is given only to institutions that ensure
proper handling according to rules and regulations. Traditional breeding
will transfer the trait into locally best adapted lines, and again will
make sure that varieties important to the poor will be used and not
fashionable varieties for the urban middle class. There will be also
direct de novo transformation into important varieties, and this will be
done with Man selection (Lucca et al., 2000). It is fortunate that the
World Bank, the Indian Council for Agricultural Research, and DBT will
probably share the costs for this development in India. Agreements have
been established with several institutions in Southeast Asia, China,
Africa, and Latin America and as soon as the written confirmation of the
"freedom to operate" is in the hands of the "Humanitarian Board," material
will be transferred.

GOLDEN RICE: THE CHALLENGE OF THE GMO OPPOSITION

A scientific breakthrough promises to add an essential dietary component
(provitamin A) to one of the major food staples of the poor and developing
world. Against all expectations, "freedom to operate" for humanitarian use
has been achieved, enabling us to provide this technology free of charge
and limitations, via national and international public research
institutions and local rice breeders to the subsistence farmers in
developing countries. Numerous rice-growing countries have expressed great
interest in embracing this novel opportunity to help reduce malnutrition,
and there is the institutional organization and the technical expertise to
further develop this technology within the rice-growing countries. Is
there any problem left that could interfere with the exploitation of
"golden rice" to the benefit of the poor and disadvantaged in developing
countries? It is unfortunate that the answer is yes: Greenpeace
(www.greenpeace.org) and associated GMO opponents regard "golden rice" as
a "Trojan horse" that may open the route for other GMO applications. As a
consequence, by their singular logic, the success of "golden rice" has to
be prevented under all circumstances, irrespective of the damage to those
for whose interest Greenpeace pretends to act. The strategy is simple and
has proven effective in Europe: undermining the acceptance of the
consumer.

"Golden rice" fulfills all the wishes the GMO opposition had earlier
expressed in their criticism of the use of the technology, and it thus
nullifies all the arguments against genetic engineering with plants in
this specific example.

Golden rice has not been developed by or for industry.

It fulfills an urgent need by complementing traditional interventions.

It presents a sustainable, cost-free solution, not requiring other
resources.

It avoids the unfortunate negative side effects of the Green Revolution.

Industry does not benefit from it.

Those who benefit are the poor and disadvantaged.

It is given free of charge and restrictions to subsistence farmers.

It does not create any new dependencies.

It will be grown without any additional inputs.

It does not create advantages for rich landowners.

It can be resown every year from the saved harvest.

It does not reduce agricultural biodiversity.

It does not affect natural biodiversity.

There is, so far, no conceptual negative effect on the environment.

There is, so far, no conceivable risk to consumer health.

It was not possible to develop the trait with traditional methods, etc.

Optimists might have expected, therefore, that the GMO opposition would
have welcomed the advent of "golden rice." The GMO opposition, however,
has been doing everything in its power to prevent "golden rice" from
reaching subsistence farmers. This is because the GMO opposition has a
hidden, political agenda. It is not so much the concern about the
environment, or the health of the consumer, or the help for the poor and
disadvantaged. It is a radical fight against a technology and for
political success. This could be tolerated in rich countries where people
have a luxurious life even without the new technology. However, it cannot
be tolerated in poor countries, where the technology can make the
difference between life and death or between health and severe illness.

However, because its acceptance has to be prevented under all
circumstances, new arguments had to be invented. Thus, the oppposition has
argued that there is no need for "golden rice" because distribution of
synthetic vitamin A works perfectly, or that nobody wants it because it
tastes awful, or that people who eat "golden rice" will lose their hair
and sexual potential! If you are interested in further misinformation of
this kind, please consult various anti-GMO Web sites on the Internet.

One is tempted to ignore these aspersions, but this would be the wrong
strategy. I am afraid that Greenpeace's specious arguments against "golden
rice" will lead to unwarranted opposition in some developing countries.
The consequence will be millions of unnecessarily blind children and
vitamin-A deficiency-related deaths. For these reasons, we have the moral
obligation to enlighten the public concerning the dangerous and immoral
game the GMO opposition is playing. Anti-GMO activists are using all their
political power (and funds collected ostensibly to protect whales and baby
seals) to prevent a humanitarian project aimed toward helping millions of
people who are malnourished and in grave danger of going blind. The GMO
opposition often demands that scientists be held responsible for their
actions. At the same time, however, they sidestep responsibility for the
harm they cause to the disadvantaged and poor with their creation of a
most hostile atmosphere against GMOs in Europe and elsewhere. In my
judgment, hindering a person's access to life- or sight-saving food is
criminal. To do this to millions of children is so criminal that it should
not be tolerated by any society. It is unfortunate that our society,
especially in Europe, is unable to recognize the true face of an
organization that is using the mask of a few idealists risking their lives
to save a few whales. The extent to which Greenpeace can act outside the
law with impunity, and how skewed the mind of a European judge can be, was
recently demonstrated in a judicial court in Nottingham, UK. The vandalism
by Greenpeace activists of a government-supported experimental plot
examining the possible effects of transgenic maize on the environment was
ruled justifiable because it had been done "in the higher interest of
mankind." In my view, the Greenpeace management has but one real interest:
to organize media-effective actions for fund raising. The "golden rice"
case hopefully may help to unmask the true and shameful face of
Greenpeace, but only if the media are willing to take them to task.

I share the optimism of Norman Borlaug (2000) concerning the potential
that GMO technology has for improving the living conditions of the poor
and underprivileged in developing countries. I admire his "standing up to
the antiscience crowd." I wish that more internationally recognized
personalities would demonstrate similar civil courage and that the
scientific community (and the granting agencies) would find a bit more
interest in contributing to solutions of the problems of food security. In
the long run, our science has the best chance to survive if we win the
support of the public. For this, it is no longer sufficient simply to do
good sciencewe must also be activists for and popularizers of the new
technology.


LITERATURE CITED

* Borlaug NE (2000) Ending world hunger: the promise of biotechnology and
the threat of antiscience zealotry. Plant Physiol 124: 487-490

* Burkhardt PK, Beyer P, Wnn J, Klti A, Armstrong G, Schledz M, von
Lintig J, Potrykus I (1997) Transgenic rice (Oryza sativa) endosperm
expressing daffodil (Narcissus pseudonarcissus) phytoene synthase
accumulates phytoene, a key intermediate of provitamin A biosynthesis.
Plant J 11: 1071-1078[Medline]

* Chrispeels MJ (2000) Biotechnology and the poor. Plant Physiol 124: 3-6

* Lucca P, Ye X, Potrykus I (2000) Effective selection and regeneration of
transgenic rice plants with mannose as selective agent. Mol Breed (in
press)

* Nash JM (2000) Grains of hope. Time, July 31, 2000, pp 38-46

* Somerville C (2000) The genetically modified organism conflict. Plant
Physiol 123: 1201-1202[Full Text]

* Ye X, Al-Babili S, Klti A, Zhang J, Lucca P, Beyer P, Potrykus I (2000)
Engineering provitamin A (-carotene) biosynthetic pathway into
(carotenoid-free) rice endosperm. Science 287: 303-305 Ingo Potrykus

Institute of Plant Sciences Swiss Federal Institute of Technology ETH
Center, LFW E 53.1 CH-8092 Zurich Switzerland Potrykus@active.ch