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Date:

June 27, 2000

Subject:

Potrykus Rebutts Attack on Golden Rice

 

AgBioView - http://www.agbioworld.org, http://agbioview.listbot.com

From: Klaus Ammann
Subject: Ingo Potrykus about the golden rice, an answer to opponents

Dear friends,

the golden rice seems to become a major threat for the radical opponents
of GT, on the ISIS site

http://www.i-sis.org/

there is a lengthy article of Mae van Ho, in which she scratches together
all sorts of assumptions in order to produce a negative picture of this
very promising crop.

Thanks to Ingo Potrykus (potrykus@active.ch) to take the time and trouble
to counter such attacks again and again.

see below Ingo's answer the original ISIS article by Mae van Ho

There is no justice in this debate: the industry and in the case of the
golden rice the two researchers need to carefully evaluate word by word in
their regulatory, patenting and publishing activity, whereas the protest
industry can produce nice websites full of erroneous statements. Nobody
holds them responsible for the damage they cause.

This is why I think it is high time to regulate the protest industry. Let
me be very clear about this: No censuring, but regulating their activity
by an independent body who creates a regujlatory framework which can be
accepted by the NGO's, a framework which must be more than just a weak
'code of conduct' as an alibi. And again: Nothing against the power of the
protest industry, it is good to have a true balance in this debate, but
everything against the hypocrisy of an unregulated wild activity of the so
called DAVID against the GOLIATH, what a joke.

Klaus
++++++++++++++++++++++++++++++++++++++++++++

Dear Klaus,

sorry for answering so late. I tend to ignore this kind of bullshit. One
can waste a lot of time with responding.

Here are the key messages from the "golden rice" work.

a) It has been developed within public research, without any connection to
industry, with public and foundation funds only.

b) It has been patented by Peter Beyer and Ingo Potrykus.

c) The technology will be given, by the inventors, free of charge and
limitations, for non-commercial (humanitarian) use in developing
countries. The definition for non-comercial is yearly profit from this
rice of $ 10 000.- annually. This allows not only free use by the
subsisstance farmer but also substantial local commecial development.

d) Commercial development (which is as important for food security in
developing countries, because there are hundreds of millions urban poor
who can not grow there own rice!) will be under licence from ASTRA Zeneca.

e) To optimize humanitarian as well as commecial use the inventors have
transferred the rights in golden rice to Greenovation which has
transferred an exclusive licence to Zeneca, which has transferred a
sublicence to the inventors for (the above defined) non-commercial use in
developing countries, which will give sub-sublicences to public research
institutions and humanitarian organizations.

f) The golden rice project was started 1990 when nobody thought that it
might help improving acceptibility of the technology 10 years later. It
was definitely not started to help the AgBiotech companies with their PR.

g) The project took 10 years to completion and the scientific community
did not believe it would work untill we could present proof of concept.

h) The "golden rice" contains provitamin A at a level just sufficient to,
hopefully, have an effect. We are working towards higher production.

i) There is not the slightest risk of overdosage, as is with synthetic
vitamin A.

j) The material will be given (free of charge and limitations for
non-commercial use), on request from governmental institutions, to public
research institutions, which guarrantee for proper handling according to
established GMO procedures.

k) The following assessments will precede release to the pubic:

1) Needs assessment to compare with alternative possibilities;
2) Bioavailability studies to study its effect;
3) Substantial equivalence to exclude surprises;
4) Toxicological assessment;
5) Allergenicity assessment;
6) Environmental impact assessment;
7) Socio.economic asessment;
8) Public acceptance;

l) The technology will only be used if all this is O.K. and the national
biosafety authorities agree release to the public

m) There is an enormous demand from developing countries to get the
technology as soon as possible.

n) The material could not yet be distributed because not only the
inventors have to give their invention, but also 32 patent holders have to
give freedom to operate
for 70 patents involved in the development. We are also bound, so far, by
MTA's for DNA's now present in "golden rice".

o) With the help of Zeneca, ISAAA and others we are trying to establish
freedom to operate. It will be necessary to do this for each individual
country.

p) The need for the technology is well documented already: despite the
proposed "traditional solutions" which are available to date (free
distribution of vitamin A, encouragement for more vegetables and fruits in
the diet) 134 million youths are vitamin A-deficient, 5 million die
annualy as consequence from VAD and 500 000 turn irreversibly blind.

q) There is no new dependency of the farmers from anybody; they are the
owners of the material, they use there own harvest for the next sowing;
they do not need any additional inputs; they have a new opportunity for
commercial development.

r) There is no effect on biodiversity because the trait will be
transferred into all the successfull rice varieties in use to date.

s) There was no "traditional" possibility to acheive the same because
there is no corresponding genetic information in the rice gene pool. t) We
are used to eat the gene poducts since hundreds of thousands of years.

u) etc, etc, etc.

Of course, if you are against genetic engineeringby principle you must
fight "golden rice" because it shows the public that the technique is good
for the consumer, the poor, the disadvantaged, and not just good for
industry and the rich.

What these radical opponents are doing is "Brunnenvergiftung" to the
disadvantage of the poor.

What I find very disturbing,is the fact, that they can play their dirty
game without having to take responsibility for what they are damaging.

By the way, I have to invest thousands of hours of my "free time" to try
to make sure that the technology really reaches the poor and disadvantaged
free and without limitations, and I am doing it without a penny of
financial return and with the continuous risk of overstretching the bow in
the relations to my wife.


With best regards
Ingo
+++++++++++++++++++++++++++++++++++++++++++++++


The Golden Rice‚ - An Exercise in How Not to Do Science


The golden rice‚ - a GM rice engineered to produce pro-Vitamin A - is
being offered to the Third World as cure for widespread vitamin A
deficiency.

The audit uncovers fundamental deficiencies in all aspects, from the
scientific/social rationale to the science and technology involved. It is
being promoted in order to salvage a morally as well as financially
bankrupt agricultural biotech industry.

The scientific/social rationalization for the project exposes a
reductionist self-serving scientific paradigm that fails to see the world
beyond its own narrow confines. The Œgolden rice‚ is a useless
application. Some 70 patents have already been filed on the GM genes and
constructs used in making the Œgolden rice‚. It is a drain on public
resources and a major obstruction to the implementation of sustainable
agriculture that can provide the real solutions to world hunger and
malnutrition.

Golden rice‚ is not a second generation‚ GM crop as has been claimed. It
involves standard first generation technology, and carries some of the
worst features in terms of hazards to health and biodiversity. Rockefeller
Foundation, the major funder of the project by far has withdrawn support
from it. The project should be abandoned altogether.

Key Words: ŒGolden rice‚, vitamin A deficiency, Green Revolution,
sustainable science, GM technology, gene patents, GM constructs


A gift-horse for the poor
A report in Financial Times states that the creators of Œgolden rice‚ have
struck Œa ground-breaking deal‚ with corporate giant AstraZeneca to give
Third World farmers free access to the grain while allowing it to be
commercially exploited in the developed world. The company will oversee
the production of stable GM line(s) and patenting, and take the lines
through field trials and commercial approval. While farmers in developed
countries will have to pay royalties, those in the Third World earning
less than US$10 000 will not. But will Third World farmers be allowed to
save the seeds for replanting? It did not say.

This Œgolden rice‚, not yet available, is already worth its weight in
diamonds. The project was funded from four sources of public finance
totaling US$100 million: the philanthropic Rockefeller Foundation, whose
mission is to support scientific research that specifically benefit the
poor, the Swiss Federal Institute of Technology, the European Community
Biotech Program and the Swiss Federal Office for Education and Science.

The announcement failed to mention that there are already 70 patent claims
on the genes, DNA sequences, and gene constructs used to make the golden
rice. Will the cost of paying royalties for the previous 70 patent claims
be added to the cost of the golden rice? Which of the royalties on the
seventy-odd patents would the Third World farmers be absolved from paying?
Rockefeller Foundation, the major funder by far, has reportedly abandoned
the project to " shift its agricultural funding focus to support research
that will have a more direct benefit to subsistence farmers"


The scientific/social rationale is fallacious Many have commented on the
absurdity of offering Œgolden rice‚ as the cure for vitamin A deficiency
when there are plenty of alternative, infinitely cheaper sources of
vitamin A or pro-vitamin A, such as green vegetables and unpolished rice,
which would be rich in other essential vitamins and minerals besides. To
offer the poor and malnourished a high-tech Œgolden rice‚ tied up in
multiple patents, that has cost US$100 million to produce and may cost as
much to develop, is worse than telling them to eat cake.

ŒGolden rice‚ was engineered to produce pro-vitamin A or b-carotene (the
substance that makes carrots orange) in the endosperm, i.e., the part of
the rice grain that remains after it has been polished. The scientific
paper started with a review of the literature to rationalize why such GM
rice is needed and of benefit for the Third World. The paper was
accompanied by an unusually long news feature entitled, ŒThe Green
Revolution Strikes Gold‚, which reinforced the rationalization for the
project, explaining the remarkable feat of technology involved and stated
that the scientists intend to make the Œgolden rice‚ "freely available to
the farmers who need it most." The last sentence in this glowing report,
however, gave the game away: "One can only hope that this application of
plant genetic engineering to ameliorate human misery without regard to
short-term profit will restore this technology to political
acceptability."

What were the reasons for the scientists to embark on the project? It is
important to know, as these reasons may have been used to persuade funders
to support the project in the first place, and funders ought to bear as
much of the responsibility.

The first reason given is that the aleurone layer (in unpolished rice) is
usually removed by milling as it turns rancid on storage, especially in
tropical areas; and the remaining endosperm lacks pro-vitamin A. The
researchers are tacitly admitting that at least some varieties of
unpolished rice will have pro-vitamin A. The reason rice is milled is to
prolong storage for export, and to suit the tastes of the developed world.
So why not give the poor access to unpolished rice? A proportion of every
rice harvest could be kept unpolished and either given freely to the poor,
or sold at the cheapest prices. But the scientists have not considered
that possibility. Unpolished rice is fact part of the traditional Asian
diet until the Green Revolution when aggressive marketing of white
polished rice created a stigma of unpolished rice. However, most rural
communities still consume unpolished rice and now that consumers have
become aware of its nutritional value, unpolished rice is becoming sought
after.

"Predominant rice consumption", the researchers claim, promotes vitamin A
deficiency, a serious health problem in at least 26 countries, including
highly populated areas of Asia, Africa, and Latin America. Some 124
million children worldwide are estimated to be vitamin A deficient.
(Actually, the latest figures quoted in a press release from the
International Rice Research Institute (IRRI) is 250 million preschool
children.) The scientists seem to be unaware that people do not eat plain
rice out of choice. The poor do not get enough to eat and are
undernourished as well as malnourished. The Food and Agricultural
Organization (FAO) started a project in 1985 to deal with vitamin A
deficiency using a combination of food fortification, food supplements and
general improvements in diets by encouraging people to grow and eat a
variety of green leafy vegetables. One main discovery is that the
absorption of pro-vitamin A depends on the overall nutritional status,
which in turn depends on the diversity of the food consumed.

"Predominant rice consumption" is most likely to be accompanied by other
dietary deficiencies. A recent study by the Global Environmental Change
Programme concludes that predominant consumption of Green Revolution crops
is responsible for iron deficiency in an estimated 1.5 billion, or a
quarter of the world‚s population. The worst affected areas are in
rice-growing regions in Asia and South-East Asia where the Green
Revolution had been most successful in increasing crop yield.

Research institutions such as IRRI have played the key role in introducing
Green Revolution crops to the Third World. IRRI was founded in 1959 under
an agreement forged by the Rockefeller and Ford Foundations with the
Philippine government, and its lease for operation expires in 2003. At its
recent 40th anniversary celebration, hundreds of Filipino rice farmers
protested against IRRI for introducing GM crops, blaming IRRI, among other
things, for promoting the Green Revolution and causing massive loss of
biological diversity in rice paddies throughout Asia.

It is clear that vitamin A deficiency is accompanied by deficiencies in
iron, iodine and a host of micronutrients, all of which comes from the
substitution of a traditionally varied diet with one based on monoculture
crops of the Green Revolution. The real cure is to re-introduce
agricultural biodiversity in the many forms of sustainable agriculture
already being practiced successfully by tens of millions of farmers all
over the world.

As the scientists know, clinical deficiency can be dealt with by
prescription of vitamin A pills, which are affordable and immediately
available. "Oral delivery of vitamin A is problematic", they state.
Judging from the reference cited they may be referring to the well-known
harmful effects of vitamin A overdose. But why would high levels of
pro-vitamin A rice in a staple food that people generally consume in the
largest amounts in a meal not also cause problems connected with overdose?
In particular, vitamin A poisoning has been known to result from excessive
b-carotene intake in food.

Finally, why is it necessary to genetic engineer rice? "Because no rice
cultivars produce [pro-vitamin A] in the endosperm, recombinant
technologies rather than conventional breeding are required." This is the
conclusion to the whole fallacious reasoning process. It amounts to this:
rice is polished, which removes pro-vitamin. A, therefore a hundred
million dollars (much of it tax-payers‚ money) are needed to put
pro-vitamin A into polished rice. A more likely explanation is that the
geneticists are looking for funding to do their research, and have
constructed, as best they could, a series of rationalizations for why they
should be supported. Neither the scientists nor the funders have looked
further beyond the technology to people‚s needs and aspirations, or to
what the real solutions are.

The science and technology is standard first generation It took ten years
to engineer b-carotene into polished rice because rice naturally does not
have the metabolic pathway to make it in the endosperm, perhaps for good
biological reasons. Immature rice endosperm makes the early precursor,
geranylgeranyl-diphosphate (GGPP). In order to turn GGPP into b-carotene,
four metabolic reactions are needed, each catalyzed by a different enzyme.
Enzyme 1, phytoene synthase converts GGPP to phytoene, which is colorless.
Enzymes 2 and 3, phytoene desaturase and z-carotene desaturase, each
catalyzes the introduction of two double-bonds into the phytoene molecule
to make lycopene, which is red in colour. Finally, Enzyme 4, lycopene
b-cyclase turns lycopene into b-carotene. Hereafter, the enzymes will be
referred to by numbers only. Thus, a total of four enzymes have to be
engineered into the rice in such a way that the enzymes are expressed in
the endosperm. Some very complicated artificial gene constructs have to be
made. The gene constructs are made in units called expression cassettes
(see Box 1)


Box 1

The Œgene expression cassette‚ ˆ a unit of transgenic construct The gene
for each enzyme never goes in alone. It has to be accompanied by a special
piece of genetic material (DNA), the promoter, which signals the cell to
turn the gene on, ie, to transcribe the DNA gene sequence into RNA. At the
end of the gene, there has to be another signal, a terminator, to mark the
RNA so it can be translated into protein. To target the protein to the
endosperm, an extra bit of DNA, a transit sequence, is required. The
resulting expression cassette for each gene is as follows:


promoter transit sequence gene terminator


Typically, each bit of the construct: promoter, transit sequence, gene and
terminator is from a different source. Several expression cassettes are
usually linked in series, or Œstacked‚ in the final construct.


In order to select for the plant cells that have taken up the foreign
genes and gene-constructs, Œgolden rice‚ makes use of a standard
antibiotic resistance gene coding for hygromycin resistance, also equipped
with its own promoter and terminator. All these expression cassettes have
to be introduced into the rice plant cells. One simplification available
is that the reactions catalyzed by two of the enzymes, 2 and 3, could be
done by a single bacterial enzyme, let‚s call it enzyme 2-3, so a total of
four expression cassettes have to be introduced, one for each of three
enzymes and the fourth for the antibiotic resistance marker.

Unlike natural genetic material which consists of stable combinations of
genes that have co-existed for billions of years, artificial constructs
consists of combinations that have never existed, not in billions of years
of evolution. Artificial gene-constructs are well-known to be structurally
unstable, which means they tend to break and join up incorrectly, and with
other bits of genetic material, resulting in new unpredictable
combinations. This process of breaking and joining of genetic material is
referred to as recombination. The more complicated the construct, the more
it tends to break and rearrange or form new combinations. The instability
of the construct means that it is seldom inserted into the plant genome in
its intended form. The inserts are generally rearranged, with parts
deleted, or repeated.

In order to make many copies of the construct and to facilitate entry into
plant cells, the construct is spliced into an artificial vector, which is
generally made from genetic parasites that live inside cells. The
artificial vector also enables the construct to be efficiently smuggled
into the plant cell and to jump into the genome of the plant cell. The
vector used in the case of the Œgolden rice‚ is the one most widely used
since the beginning of plant genetic engineering. It is derived from the
ŒT-DNA‚, part of the tumor-inducing (Ti) plasmid (a genetic parasite) of
the soil bacterium, Agrobacterium. The Ti plasmid naturally invades plant
cells, inserting the T-DNA into the plant cell genome, and causing the
cell to develop into a plant tumor or gall. The artificial gene construct
is spliced in between the left and right borders of the T-DNA vector. The
borders of the T-DNA are Œhotspots‚ for recombination, ie, they have a
pronounced tendency to break and join up, which is ultimately why the
vector can invade the plant‚s genome and carry its hitch-hiker gene
construct along with it.

Three different constructs were made. The first consists of the expression
cassettes of enzyme 1 from daffodils and enzyme 2-3 from the plant
bacterial pathogen, Erwinia uredovora, together with the expression
cassette of an antibiotic resistance marker gene that codes for hygromycin
resistance. Another antibiotic resistance gene (coding for kanamycin
resistance) is also present, albeit lacking a promoter. Hygromycin and
kanamycin are both aminoglycoside antibiotics that inhibit protein
synthesis. The resistance genes originate from bacteria and generally have
specificities for more than one aminoglycoside antibiotic. This first
construct is the most complicated, but it still does not have all the
required enzymes. Enzyme 1 and the hygromycin resistance gene are both
equipped with a promoter from the cauliflower mosaic virus (CaMV), which
is especially hazardous (see below).

The second construct consists of the expression cassettes of enzyme 1 and
enzyme 2-3 as in the first, but without any antibiotic resistance marker
genes. The third construct consists of the expression cassette of enzyme
4, again from daffodil, stacked with the hygromycin-resistance marker-gene
cassette. The strategy of separating the genes for the enzymes and
antibiotic resistance marker into two different constructs is that it
overcomes some of the problems of structural instability: the more
cassettes stacked, the more unstable is the construct.

Each construct was spliced into a T-DNA vector, and two transformation
experiments were carried out. In the first experiment, 800 immature rice
embryos were inoculated with the vector containing the first construct,
and hygromycin was used to select for resistant plants that have taken up
the vector, resulting in 50 GM plants. In the second experiment, 500
immature embryos were inoculated with a mixture of the vectors containing
the second and third construct respectively. Selection with hygromycin
gave rise to 60 GM plants that have taken up the third construct, but only
twelve of these had taken up the second construct as well. The
transformation process is well-known to be random, as there is no way to
target the foreign genes to precise locations in the genome. There could
be more than one site of insertion in a single cell. Furthermore, as
mentioned earlier, the actual inserts are likely to be rearranged, or
subject to deletions or repetitions. Hence each transformed cell will have
its own distinctive pattern of insert(s), and each GM plant, which comes
from the single transformed cell, will differ from all the rest.

Note that the GM plants from the first experiment will not have the full
complement of enzymes required to make b-carotene, and should give red
endosperm from the lycopene present. Only the GM plants from the second
experiment which have taken up both vectors would possess all the enzymes
needed, and give orange-colored endosperm.

Uncontrollable technology and unpredictable outcomes raise questions on
safety Unexpectedly, transgenic plants from both transformation
experiments gave orange polished grains. Chemical analyses confirmed that
only b-carotene, in varying amounts, was found in all lines, but no
lycopene. This suggests that enzyme 4 may be present in rice endosperm
normally, or it could be induced by lycopene, to turn all of the lycopene
into b-carotene. Lutein and zeaxanthin, two other products derived from
lycopene, were also identified in varying amounts besides b-carotene. All
of these were absent from non-GM rice.

In addition, many other uncharacterized, unidentified products were found,
which differ from one line to another. What is the nutritional value of
the other products? Are any of the known and unknown products harmful?
Without thorough chemical analyses and toxicity tests, it is impossible to
tell. This highlights the unpredictable, uncontrollable nature of the
technology.

Molecular analyses of the GM inserts were not done in any detail.
Nevertheless, judging from the evidence presented, there are the usual
signs of deletions, rearrangements and multiple repeats of the constructs
inserted due to structural instability of the constructs and the tendency
for recombination. There is no guarantee that any of the plants will give
stable progeny in successive generations. The instability of GM lines is
well-known, and is a continuing problem for the industry. Inserted genes
can lose their activities or become lost altogether in subsequent
generations. There is nothing in Œgolden rice‚ to distinguish it from
standard first generation GM plants with all the well-known defects and
hazards.

Œ Golden rice‚ is no technical improvement and more unsafe ŒGolden rice‚
exhibits all the undesirable, hazardous characteristics of existing GM
plants, and in added measure on account of the increased complexity of the
constructs and the sources of genetic material used. The hazards are
highlighted below.

It is made with a combination of genes and genetic material from viruses
and bacteria, associated with diseases in plants, and from other non-food
species.

The gene constructs are new, and have never existed in billions of years
of evolution

Unpredictable by-products have been generated due to random gene insertion
and functional interaction with host genes, which will differ from one
plant to another.

Over-expression of transgenes linked to viral promoters, such as that from
CaMV, exacerbates unintended metabolic effects as well as instability (see
below). There are at least two CaMV promoters in each transgenic plant of
the Œgolden rice‚, one of which is linked to the antibiotic resistance
marker gene.

The transgenic DNA is structurally unstable, leading to instability of the
GM plants in subsequent generations, multiplying unintended, random
effects.

Structural instability of transgenic DNA increases the likelihood of
horizontal gene transfer and recombination.

Instability of transgenic DNA is enhanced by the CaMV promoter, which has
a recombination hotspot, thereby further increasing the potential for
horizontal gene transfer.

The CaMV promoter is promicuous in function and works efficiently in all
plants, in green algae, yeast and E. coli. The spread of genes linked to
this promoter by ordinary cross-pollination or by horizontal gene transfer
will have enormous impacts on health and biodiversity. In particular, the
hygromycin resistance gene linked to it may be able to function in
bacteria associated with infectious diseases.

Horizontal transfer of transgenic DNA from GM plants into soil fungi and
bacteria has been demonstrated in laboratory experiments. Recent evidence
suggests that it has also taken place in a field-trial site for GM
sugar-beets, in which transgenic DNA persisted in the soil for at least
two years afterwards.

Prof. Hans-Hinrich Kaatz from the University of Jena, has just presented
new evidence of horizontal gene transfer within the gut of bee larvae.
Pollen from GM rapeseed tolerant to the herbicide glufosinate were fed to
immature bee larvae. When the microorganisms were isolated from the gut of
the larvae and examined for the presence of the gene conferring
glufosinate resistance, it was found in some of the bacteria as well yeast
cells.

All cells including those of human beings are now known to take up genetic
material. While natural (unmanipulated) genetic material is simply broken
down to supply energy, invasive pieces of genetic material may jump into
the genome to mutate genes. Some insertions of foreign genetic material
may also be associated with cancer.

Horizontal transfer of genes and constructs from the Œgolden rice‚ will
spread transgenes, including antibiotic resistance genes to bacterial
pathogens, and also has the potential to create new viruses and bacteria
associated with diseases.
Conclusion
In conclusion, the Œgolden rice‚ project was a useless application, a
drain on public finance and a threat to health and biodiversity. It is
being promoted in order to salvage a morally as well as financially
bankrupt agricultural biotech industry, and is obstructing the essential
shift to sustainable agriculture that can truly improve the health and
nutrition especially of the poor in the Third World. This project should
be terminated immediately before further damage is done.

The Œgolden rice‚ possesses all the usual defects of first generation
transgenic plants plus multiple copies of the CaMV promoter which we have
strongly recommended withdrawing from use on the basis of scientific
evidence indicating this promoter to be especially unsafe. A growing
number of scientists (318 scientists from 39 countries to-date) are
calling for a global moratorium on the environmental releases of GMOs
until and unless they can be shown to be safe.

Acknowledgement
I am grateful to Joe Cummins for helpful comments and for supplying key
references in preparing this audit.



Prof. Dr. Klaus Ammann
Director Botanical Garden,
University of Bern
Altenbergrain 21
CH - 3013 Bern, Switzerland
Tel. +41 31 631 49 37
Fax +41 31 631 49 93
klaus.ammann@sgi.unibe.ch