AgBioView - http://www.agbioworld.org
Three plant scientists are among the 72 who have just been elected as new
members to the prestigious National Academy of Scinces, USA. They are (1)
ROBERT BRUCE GOLDBERG ; Distinguished Professor of Biology, department of
molecular, cell, and developmental biology, University of California, Los
Angeles; (2) PATRICIA ZAMBRYSKI, professor, department of plant and
microbial biology, University of California, Berkeley; and (3) ENRICO
SANDRO COEN, deputy head, department of genetics, John Innes Centre, and
John Innes Foundation Professor, University of East Anglia, Norwich (U.K.)
as a foreign associate.
Agbioivew congratulates these pioneers for their well deserved honor. Of
course, readers of this list are familiar with Bob Golberg.
Update to mutant varieties list
- From: Alan McHughen
In his piece in AGBIOVIEW on mutant crop varieties, Prof. Morandini kindly
cited 'Pandora's Picnic Basket' for the number of crop varieties produced
using mutation breeding. However, the real authorities on officially
released mutant crop varieties are M. Maluszynski, K. Nichterlein, L.
VanZanten and B.S. Ahloowalia, who published the FAO/IEAE mutant variety
database in December, 2000. The FAO/IAEA Mutant Varieties Database .pdf
(caution- it's a large document!- 1808 kb) is available on the 'net at
Incidentally, while Pandora reported 'over 1400' mutant crop varieties,
the current number (as of last December, according to the FAO/IEAE report)
is 2252, showing mutation breeding is still a popular method of producing
improved crops. -- Best wishes, Alan
Horrors of Horizontal Gene Transfer
- From: firstname.lastname@example.org
Horizontal Gene Transfer (HGT) seems to be a hot topic suddenly, and I
have a few questions I'd like to pose to the experts. I realize the
questions are profoundly speculative.
1. With the possible exception of Archaea, it appears that all living
things on the planet have a great deal of DNA in common. For instance,
I've heard that even between humans and parsley, the DNA is about 40
percent identical. Since this points to a common ancestry for most life,
is there really a valid distinction distinction between HGT and "vertical"
gene transfer in cases where, for instance, a petunia gene is transferred
to its (albeit remote) relative, the soybean?
2. There is evidence that at least some bacteria use a Lamarckian form of
evolution, i.e., under environmental stress, during multiplication they
induce mutations in a non-random way, yielding a disproportionate number
of favorable mutations. Some bacteria are also fond of swapping handy bits
of DNA from their cousins. Does this indicate that, at least at one if not
more levels, nature long ago found HGT to be a handy mechanism for
speeding evolution and speciation? Could bacteria be the prime natural
generators of novel sequences?
3. Does the "junk" DNA found in so many organisms indicate the existence
of a mechanism designed to take advantage of HGT, which may have actually
incorporated unhelpful (or temporarily helpful) sequences over the
4. Is it possible that the system is designed to balance HGT and
speciation? Speciation into groups of organisms which are not
cross-fertile would allow them to stably exploit different ecological
niches across generations with only minimal random mutations; HGT,
however, through such media as bacteria or viruses, would make the
nearly-identical DNA of non-interfertile plant species a handy thing, by
making it easier to borrow and incorporate "working" DNA from others at
times--which would be far superior to relying simply on random mutations
for evolution. Might the system work this way? Are there any studies which
suggest this? Wouldn't this make HGT more than merely an accidental
phenomenon, but also a beneficial design feature?
5. If HGT is a functional part of evolution and plants actually "like" it,
should it really be all that scary for some people?
- From: email@example.com
The only version I saw was the attached. It is clearly a spoof.
Completely fabricated. Pretty funny I thought.
Charles Margulis: "That's, like, really uncool."
Larry Bohlen: "I knew something was going on. I mean, how else could
they make those seedless grapes?
Jane Rissler: "Compared to these plants, genetically modified food is
about as dangerous as a one-legged man in an ass-kicking contest."
"A botanist at the University of Agricultural Rationalism called the
safety concerns brought up by environmentalist groups to be completely
Note from Prakash: The forwarded posting entitled "CALL MADE TO BAN PLANT
PRODUCTS DERIVED THROUGH RADIATION: 'Mutant plants' potentially more
dangerous than biotech foods' dated May 10, 2001 from ROME (Reuters) is a
hoax and a joke posted on some newsgroups by an individual who wanted to
create some mischief and fun. It should not be taken seriously!!
Protesters Vandalize Property At Greensboro Business
Associated Press May 14, 2001
GREENSBORO, N.C. (AP) _ Three protesters face charges and others were
pepper-sprayed as a result of a demonstration Monday at a biotechnology
Protesters from the environmental groups Uwharrie Earth First! and
Southeast Resistance Against Genetic Engineering demonstrated at biotech
company Syngenta. The demonstration was "very peaceful," said company
spokeswoman Kay Carter, though she said some company signs were spray
painted. Authorities closed part of nearby Interstate 40 during rush hour
because of the protest, but reopened it a short time later.
The three people arrested were charged with vandalism, resisting arrest
and obstructing justice, Police Capt. Hugh Armstrong said. Some protesters
were sprayed with pepper gas when they tried to free their arrested
colleagues from police custody, Armstrong said. None was seriously injured.
"We certainly support the right of these individuals to express their
views," Carter said. "We also believe they have to do so in a lawful
manner." Security guards notified police about 7 a.m. when several dozen
protesters showed up outside the company, dressed in white biohazard suits
and carried signs with messages including "Stop Biotechnology."
Protester Olivia Cramer admitted that the group was trespassing, but said,
"We feel like we have a right to do that in this situation." Pollen from
genetically engineered plants sold by biotech companies has gotten into
fields of unaltered crops on adjoining fields, she said.
We Need Have No Fear Of Interference With Nature:
Emotion Is Stopping Us Embracing The Benefits Of Gene Manipulation
Mary Warnock, The Guardian May 15, 2001
When Prince Charles, in his Reith lecture last year, rebuked biologists
for drawing society into an area which 'belonged to God and God alone',
urging them to try, if they wished, to understand nature, but not to
change it, he drew a response from many confused and vaguely frightened
people. The new biotechnology seems to have opened up possibilities of
changing the genes of plants and animals in a way which nature, or God as
the creator, never intended.
Prince Charles is no fool. He did not need his father or his sister to
point out, as they did, that human beings had been interfering with nature
as long as they had sown crops for their own use, or bred cattle for milk
or meat. But he contrasted producing genetically modified crops with
traditional methods of agriculture which have stood the test of time
because 'they are working with the grain of nature'. Which way does
nature's grain lead us? Human nature is thought to be determined by its
genes, genes which may be shared across all species from the lowly fruit
fly to plants themselves. So are those who fear that genetic manipulation
is a threat to nature simply expressing their outrage at the diminution of
the status of man, his now unspecial place in nature, as the Victorians
did in the great rows of the 19th century with the church?
I do not think so. After all, many people who probably believe in no gods
at all nevertheless accuse biological scientists of seeking to 'play God'.
In this country at least there are not many who would deny the theory of
evolution. The argument has moved on; and those who object that genetic
manipulation is against nature are not merely re-enacting the passionate
disputes of earlier times, for they accept most of the Darwinian premises.
The fear that lies behind the objections seems to be a fear that the laws
of nature themselves are no longer to be relied upon. Jonathon Porritt,
former director of Friends of the Earth, wrote in his book Playing Safe
that 'the hard lines between different organisms and species are beginning
to melt away. We can now pick and choose individual genes from one
organism to introduce into a totally different and unrelated organism,
crossing all biological boundaries in combinations that nature never could
and never would bring together.'
In a society which we are constantly reminded is 'plural' - no one set of
moral principles or even laws being better or more valid than any other -
it seems particularly terrible if the certainties of laws of nature itself
can be eroded. It was upon such fears that, Mary Shelley played, as long
ago as 1818, in her story Frankenstein or the New Prometheus. She
deliberately sought to 'speak to the mysterious fears of our nature, and
awaken thrilling horror'.
This was the myth of an unnatural creature being formed in the laboratory
whose growth and behaviour could not be controlled. In the 1920s, we had
the myth of Aldous Huxley's Brave New World, in which races of creatures
could be produced who would be all too well controlled, who would be
designed indeed to fulfill specific functions. Both myths, not so much
scientific as social and political, certainly inspire terror, and both
live on in the kind of language used of biological scientists.
Our attitude towards nature is complex and has a history; the word itself
has resonances which are strongly influenced both by the attitude of
respectful observation of nature and that of the romantic searching of
nature for our own proper dwelling, for where we feel that we most deeply
belong. Both of these attitudes derive from the change in sensibility that
came about roughly at the time of the French revolution, the end of the
Age of Enlightenment.
It would be impossible for us to free ourselves from such attitudes if
only because of the immense influence on us that is exercised by European
and American art of the period. Nor do I suppose that many of us would
want to be rid of them, since for many they afford the greatest pleasures
in life. But we are also subject to the influence of Darwinian biology,
and the new way in which we have been taught to think of nature as one
organism, whose 'building blocks', as we are frequently told, are genes.
In such a world, we are confronted not only by science which has
discovered and will discover more and more about how these genes work,
with one another and with their environment, but also by increasingly
sophisticated technology, needed both for the discoveries themselves and
for any interventions which agriculturists or doctors may decide to
undertake. It is doubtless prudent to be fairly cautious in what
interventions there should be. But a modest conservatism does not entail
that nothing new should ever be tried. Nor do I believe that the resonance
and emotive force contained in the word 'nature' should have any power to
influence the decisions of society as to what is or is not an acceptable
If it can be shown, as I believe it can, that the genetic modification of
rice to make it more tolerant of adverse weather conditions would make a
great difference to the level of nutrition in countries where rice is the
most important element of diet, then common humanity demands that such
modified rice should be made accessible. If it can be shown that nuclear
cell transplant (and thus the transplant of genes) can effectively restore
someone's damaged liver, brain or spinal cord, then the common
humanitarian concerns which have always been the concerns of medicine
should be permitted to develop the technology necessary for such treatment.
That it is perhaps 'against the grain of nature' is no more relevant an
argument against it than it would be to claim that a replacement hip joint
is against the grain of nature. There is just one hypothetical case in
which I might myself be inclined to use the argument that a development
was, in an injurious sense, 'against nature'. This would be the case where
someone decided that if one cell in a human or other animal body could be
replaced and regenerated then all the cells could be so treated again and
again, so that the person or animal never died.
I would argue that all our attitudes to nature, all our love and respect
for it depend on its ephemeral, or at least fragile, essence. And this
fragility of course extends to our notion of ourselves. If prolonging our
lives indefinitely were really on the cards, then I for one would wish to
legislate against it on the grounds that all men are mortal, and to deny
this would be to deny our very understanding of the world.
The author is a member of the Lords. Extracted from a lecture at Gresham
College. Baroness Warnock
The Green Revolution Yields to the Bottom Line
By ANDREW POLLACK, New York Times, May 15, 2001
Dr. William Folk, a professor at the University of Missouri, wants to
genetically engineer soybeans to improve their nutritional value. But he
faces more than scientific hurdles. He and Monsanto never agreed on how he
might use a patented technique for inserting genes into the beans.
"These procedures that have by and large been most useful are now
inaccessible," Dr. Folk said.
Dr. Folk is feeling the effects of a major change engulfing agricultural
research. Once the realm of public institutions like land-grant colleges,
it is increasingly being controlled by private companies.
This fundamental shift alarms some farming experts, who point out that the
public research system trained thousands of farmers over the decades and
vastly improved farm output both in the United States and overseas. Now,
these critics say, patent restrictions are choking the free exchange of
seeds and technology that nourished the public system. Research on
potential crop improvements has been delayed or abandoned. And in the
quest for profits, crop development for poor countries could be neglected.
Scientists at the University of Costa Rica, for example, have genetically
engineered rice to provide resistance to a virus that is a major problem
in the tropics. But before the university can sell the seeds to farmers,
it must get clearance from holders of as many as 34 patents, said Dr. Ana
Sittenfeld, an associate professor there.
In the United States, about 45 percent of plant breeders at universities
said that trouble getting seeds from private companies interfered with
their research, according to a 1999 survey by Steven C. Price, director
for industry relations at the University of Wisconsin. "The things that
give us a safe and healthy food supply are slowly eroding," said Dr.
Samuel H. Smith, the former president of Washington State University, who
is trying to secure more financing for land-grant colleges like his own.
"It's a slow death."
Seed companies and other agricultural experts dismiss any safety concerns
or say they are overstated. And, they say, the private sector influx has
brought with it new technology and increased total research spending.
"Nobody was investing any serious money in improving soybeans until there
was intellectual property protection," said Dr. Tony Cavalieri, a vice
president at Pioneer Hi-Bred International.
But some critics say companies are overemphasizing genetic engineering
because it is easier to protect engineered crops with patents. That is
risky, they say, because consumers may reject bioengineered food. Nor is
it certain that biotechnology will improve crop output the way classical
breeding has. "I am worried we are getting off the proven thoroughbred too
quickly to get on a highly decorated donkey," Dr. Margaret Mellon of the
Union of Concerned Scientists said.
Others worry that a small group of companies could control the world's
food supply. Such concerns were heightened in January when two companies
announced they had determined the genetic code of rice, years ahead of a
government effort. "One thing people could argue is, How can a company own
the most important food crop in the world?" said Dr. Rod A. Wing of
Clemson University. "In Asia, rice is like a religion. To own a religion,
so to speak, that's just a question. Can you do that? I don't think so."
The shift from public to private research was spurred by court and patent
office decisions in the 1980's that allowed plant varieties and genes to
be patented. The rulings meant that companies could more easily recoup
investments in improved crops. And with the advent of biotechnology,
advanced research now requires tools that some public institutes cannot
afford, like gene databases. At the same time, growth in government
spending on farm research has slowed as fears of widespread hunger have
abated. In industrialized countries, public spending has been growing 1.8
percent a year and private spending 5 percent, according to Philip G.
Pardey, a senior research fellow at the International Food Policy Research
Institute in Washington.
The United States Department of Agriculture's research budget, about $2
billion a year, has barely grown in real terms over two decades. Britain
has privatized some government agricultural research centers. And some
developing countries have actually cut research spending.
In the United States, private agricultural research spending surpassed
public spending in the early 1980's, and the gap has widened. By 1994,
two-thirds of American plant breeding was in the private sector, according
to an Iowa State University survey that is still considered authoritative.
"Breeders in the public sector have essentially vanished," said Dr.
William F. Tracy, professor of agronomy at the University of Wisconsin.
If public breeding withers, perhaps the biggest concern is that the
improvement of crops for the developing world will falter because of low
profit potential. "It's the same phenomenon with the malaria vaccine,"
said Dr. Hubert Zandstra, director general of the International Potato
Center in Peru, which is supported by governments and charities. "Why is
there no malaria vaccine? Because there's no one to pay for it."
Dr. Zandstra said seed companies hesitated to develop virus-resistant
potato seeds because the harm done by viruses forced farmers to buy new
seeds. But with his center developing such seeds, companies are following
so they don't lose sales. Even in wealthy countries, companies are not
likely to devote much effort to minor crops. A further concern is that a
wave of acquisitions has left much of the seed business and most
agricultural biotech patents in the hands of five big companies: Monsanto;
Syngenta; DuPont, which bought Pioneer Hi- Bred; Dow Chemical; and Aventis.
Some smaller companies also worry about this trend. "If the companies are
making all those discoveries they may lock them up," said Dr. Jerry
Caulder, chief executive of the Akkadix Corporation, an agricultural
biotech start-up. "If our universities were doing it, then literally
thousands of new companies could be created."
Even at universities, a small but growing portion of research is being
conducted by companies. In 1998, Novartis, now known as Syngenta, agreed
to give $25 million over five years to the plant and microbial biology
department at the University of California at Berkeley in exchange for
first rights to licensing some department discoveries. While critics on
campus say the deal threatens academic freedom, the university argues that
it gets needed money and access to crop gene databases that are needed for
plant research but which it cannot develop on its own.
The old breeding technique of crossing two plants rarely involves patents.
But the modern equivalent ? inserting a gene into a plant ? can involve
numerous patented technologies, including the gene itself, the insertion
method, the "promoter" that turns the gene on and the marker used to
detect whether the gene is present. Golden rice, an experimental crop that
might one day help alleviate vitamin A deficiency, which can cause
blindness, was covered by as many as 70 patents owned by 31 companies or
universities in various countries. The patent holders have agreed to
charge no royalties for rice that is to be given free to poor farmers in
developing countries. But the licensing process delayed work on the rice
by about a year.
Hoping to garner public support for genetically modified foods, the
biotech companies say they are willing to allow their technologies to be
used for humanitarian purposes. Some companies insist the process is less
than overwhelming. "Is it more of a hassle? Yes," Dr. Robert T. Fraley,
chief technology officer of Monsanto. "Is it a real barrier? I don't think
so." Monsanto usually allows university scientists to use its technology
for research, executives said, though a separate license may be required
for commercial use. Dr. Folk of the University of Missouri planned
commercial use for the soybean seeds he developed, so he was treated like
a competitor and asked for a detailed proposal, which he did not provide,
a Monsanto spokesman said.
But some scientists say having a license only for research is not enough.
California strawberry growers canceled a project to develop a strawberry
resistant to fungus for fear that they would not be allowed to let the
strawberry be grown commercially, said Dr. Alan Bennett, executive
director of the office of technology transfer at the University of
California, which discovered the fungal resistance gene.
In some cases, companies let academic scientists use their technology in
return for commercial rights to any results. And universities themselves
are now patenting their inventions ? and often licensing them to
companies. The result is that companies are capturing the output of public
sector research, said Dr. Gary Toenniessen, director for food security at
the Rockefeller Foundation.
The gene that spurred the green revolution in the 1960's ? creating
high-yield grain and helping alleviate world hunger ? was provided to Dr.
Norman E. Borlaug by Washington State University. "If that happened
today," he said, "Washington State would take out a patent and license it
to DuPont or Monsanto or somebody." The International Rice Research
Institute in the Philippines spent 11 years narrowing the search for a
gene to make rice resistant to leaf blight. It gave its work to the
University of California at Davis, which found the gene and patented it.
But before it could use the gene to develop blight-resistant rice for poor
farmers, the institute needed a license from Davis, and that license took
three years to get.
As companies and universities patent improved varieties, developing
countries, which harbor many wild seeds useful in breeding, are growing
reluctant to share these seeds without compensation. Barley from Ethiopia
imparted virus resistance to California's crop in the 1950's, without any
compensation to Ethiopia.
But such free exchange, which nourished world agriculture for decades, is
becoming a thing of the past. Now, farmers and public researchers hope to
reclaim lost ground. A new lobbying group, the National Coalition for Food
and Agricultural Research, held its inaugural meeting in January. It
attracted about 50 individuals and institutions including farmers, farm
groups like the American Soybean Association, university scientists and
companies like Monsanto, which benefit from the scientific advances and
training provided by the public sector.
Terry L. Wolf, a farmer from Homer, Ill., who is president of the
coalition, said increased research was needed for American agriculture to
remain competitive in world markets. "Most new innovation that has come
about in the last 50 years has come from the public sector," Mr. Wolf said.
The voices are being heard somewhat. The Agriculture Department's budget
is up 11 percent this year. However, President Bush's budget for next year
would increase the department's main research program by only $1 million,
to $916 million, and would cut other research programs. It is difficult to
argue for more funding when farmers suffer from crop surpluses, when
obesity seems a bigger problem than malnutrition and when medical research
has more ardent advocates.
"It's a real poignant testimony for a youngster to come in and say, `We
need more funding or I'm going to die,' " said Barbara Glenn, chairwoman
of CoFARM, a coalition of professional societies pushing for more
agricultural research. "No one's dying from starvation. It's a really hard
argument to make." Some academic experts say that ultimately the best hope
for the public sector is to tap into the money and technology of the
private sector. The companies now seem more willing to enter into such
partnerships, in part to avert criticism of biotechnology and in part
because the sequencing of crop genomes is providing too much information
for the companies to analyze alone.
"Perhaps the private sector is more willing to have public institutions
working with them, whereas in the past they didn't need us," said Dr.
Victor Lechtenberg, dean of agriculture at Purdue. Right now each
licensing deal has to be arranged separately, a cumbersome process.
Scientists met in Berkeley in February to discuss setting up a patent
exchange on the Internet. Still, some say that even faster licensing is no
substitute for the old ways. "Improvements will slow with the loss of free
exchange," said Dr. Tracy of the University of Wisconsin. "That's just
Do Plants Have More Genes Than Humans?
- Joachim Messing, Trends in Plant Science, 6:5:195-1 May 2001 96 (Via
The most surprising outcome of sequencing the human genome is the small
number of predicted genes. Both the International Human Genome Sequencing
Consortium and Celera Genomics came to similar conclusions, with
estimations of 31 000-32 000 genes 1,2 . However, how much of the actual
genome has been sequenced remains speculation because the sequence is in
draft form and is not completely contiguous. Therefore, the total number
of genes could be higher. The small number of predicted genes was
surprising given the large collection of human cDNAs. This discrepancy
could be because of post-transcriptional, rather than transcriptional,
control of gene function, which can be accomplished by alternative
splicing. Indeed, many of the sequenced human genes have alternative
splice products. In addition, several other processes (e.g. signal
transduction) proceed via further protein modifications, such as
glycosylation. Therefore, the number of human protein products could far
exceed the number of genes. Interestingly, although it is only
one-thirtieth the size of the human genome, the predicted number of genes
in Arabidopsis thaliana (25 500) is in the same league as the predicted
number of human genes 3 . Because both genomes show evidence of
genome-wide segmental duplications, this is unlikely to explain the
difference in genome size. Alternatively, because the majority of the
human genome appears to have expanded intergenic regions, with
retroelements as the predominant species, likewise the size variation
among plant genomes [some of which are even larger than the human genome
(e.g. barley, wheat)] could be because of the insertion of transposable
elements into intergenic regions. Although this is a possibility, it might
be too simplistic a view, discounting a fundamental difference between
plants and animals in the evolution of their gene regulatory mechanisms.
Borlaug Featured at London Conference
A major international biotechnology conference will be held in London May
31-June 1 and will feature Norman E. Borlaug, agronomist and Nobel
laureate. Borlaug says he is among the majority of agricultural scientists
who believes there are "great potential benefits" coming from
biotechnology in coming decades.
In an abstract of his address to the conference, Borlaug says, "The more
pertinent question today is whether scientists will be allowed to harness
the power of recombinant DNA and whether the world's farmers and ranchers
will be permitted access to the new agricultural biotechnologies so that
they can be brought to fruition in future food, feed, fiber, and livestock
Titled "Seeds of Opportunity," the conference is sponsored by the School
of Oriental and African Studies and Queen Mary College, both part of the
University of London, the Royal Agricultural College, Cirencester and the
U.S. Embassy. A news release on the entire conference is on the Internet
Despite the successes of the Green Revolution, says Borlaug, the battle to
ensure food security for hundreds of millions of miserably poor people "is
far from won." He continues, "Mushrooming populations, changing
demographics, inadequate poverty-reduction programs, and environmental
abuses have all taken their toll on world agriculture. Indeed, enormous
challenges lie ahead to ensure that the projected world population of the
8.3 billion people in 2025 is adequately and equitably fed, and in
environmentally sustainable ways."
Over the last 20 years, biotechnology based upon recombinant DNA has
developed "invaluable new scientific methodologies and products for food
and agriculture," he adds. Recombinant DNA methods have enabled breeders
to select and transfer single genes, not only reducing the time needed in
conventional breeding to eliminate undesirable genes but also allowing
breeders access to useful genes from other distant species.
"So far, agricultural biotechnology has mainly conferred producer-oriented
benefits, such as resistance to pests, diseases, and herbicides. But many
consumer-oriented benefits, such as improved nutritional and other
health-related characteristics, are likely to be realized over the next 10
to 20 years," according to Borlaug.
Moreover, during the past 40 years, "sweeping changes have occurred in
food production in the Third World," says Borlaug. In developing Asia
alone, the adoption by farmers of modern varieties and improved crop
management practices has allowed rice and wheat production to increase
from 127 million to 762 million tons from 1961 to 2000, a period in which
population grew from 1.6 to 3.5 billion people.
A copy of Borlaug's abstract is on the Internet at
UN FAO Head Sees Biotech Foods Boosting Yields, Quality
LONDON -(Dow Jones)- The director general of the United Nations Food and
Agriculture Organization said Monday that biotechnology and genetically
modified organisms can increase the supply, diversity and quality of food
products and reduce costs of production and environmental degradation.
In a press release, the FAO said Jacques Diouf made his remarks in a
speech in Stockholm to an international conference on genetically modified
crops. However, Diouf said consumers must still be given the right to an
informed choice in what they consume. He also said that in light of the
"fundamental ethical responsibility" of scientists, each application for
genetically modified organisms must be considered on a case-by-case basis.
"The right to informed choice derives from the ethical concept of the
autonomy of individuals," Diouf said. "This principle can be applied, for
example, in the debate on labeling food derived from genetically modified
organisms to ensure that consumers know what they are consuming and are
able to make informed decisions."
Diouf said now that yield ceilings have been reached in conventional plant
breeding programs, biotechnology and genetic engineering could help boost
yields. "We can no longer depend on bringing significant new areas of
virgin lands into the food production chain and further expansion of food
production must come from increased yields on the lands already farmed by
the poorest of small farmers and the larger farms alike," Diouf said.
He said "Golden Rice," which has been genetically modified to produce
vitamin A and has increased levels of iron, is "perhaps the most
significant genetic engineering breakthrough which has direct relevance to
malnutrition and food insecurity." The rice has recently been at the focus
of the debate over the safety of and need for genetically modified foods.
From: "Soule, George"
I am forwarding to you for possible inclusion on your website
www.agbioworld.org, a paper entitled "Vitamin A Deficiency Disorders:
Origins of the Problem and Approaches to Its Control" by Alfred Sommer,
MD, MHS. Dr. Sommer is dean of The Johns Hopkins University Bloomberg
School of Public Health. The paper comes to us by way of Dean Sommer.
Regards, George Soule
George Soule . Office of Communication The Rockefeller Foundation . 420
Fifth Avenue . NY, NY 10018 Tel. 1.212.852.8456 Fax 1.212.852.8441
www.rockfound.org; Committed to enriching and sustaining the lives and
livelihoods of poor and excluded people throughout the world.
"Vitamin A Deficiency Disorders: Origins of the Problem and Approaches to
- Alfred Sommer, MD, MHS;
The announcement that Swiss scientists had genetically modified a strain
of rice to produce beta-carotene, a precursor of vitamin A, set off heated
debate between those who believe this would solve the global problem of
vitamin A deficiency and those who argue that such genetically engineered
products might do more harm than good. Neither extreme is tenable. If ?
and it remains a big ?if? ? ?golden rice? and its variants prove safe and
effective, they will be a valuable new tool for controlling vitamin A
deficiency. Under the most optimistic of circumstances, however, they will
never solve the global problem by themselves. This review attempts to
place this new tool in perspective.
Vitamin A deficiency disorders encompass the full spectrum of clinical
consequences associated with suboptimal vitamin A status.(1) These
disorders are now known to include reduced immune competence resulting in
increased morbidity and mortality (largely from increased severity of
infectious diseases); night blindness, corneal ulcers, keratomalacia and
related ocular signs and symptoms of xerophthalmia; exacerbation of anemia
through suboptimal absorption and utilization of iron; and other
conditions not yet fully identified or clarified (e.g., retardation of
growth and development).(2)
Magnitude and Distribution
Clinical and sero-epidemiologic studies and surveys indicate that vitamin
A deficiency is widespread throughout the developing world. Vitamin A
deficiency has long been recognized in much of South and Southeast Asia
(India, Bangladesh, Indonesia, Vietnam, Thailand, the Philippines) by the
common presentation of clinical cases of xerophthalmia (night blindness to
permanently blinding keratomalacia). Subsequent studies in Africa, where
it had been less well recognized, indicated that a large proportion of
pediatric blindness was due to acute deterioration in vitamin A status
during measles and similar childhood infections.(3, 4)
Vitamin A deficiency was found to increase childhood morbidity and
mortality(2, 5-10) in populations in which xerophthalmia was not readily
recognized(11) and in greater numbers than would be expected solely from
the increase in mortality associated with xerophthalmia.(2, 12) This
discovery led to the recognition that seemingly mild biochemical
deficiency, insufficient to cause xerophthalmia, accounts for large
numbers of preventable childhood deaths.
The extent and distribution of vitamin A deficiency and its consequences
are remarkably well established. Numerous local and national surveys have
been conducted. In countries where they have not been conducted, data from
nearby countries with similar characteristics (under-5-year mortality,
poverty, diet) allow for judicious extrapolation. The few intensive
national surveys linked to longitudinal studies(13) and extrapolations
from sero-surveys and community-based randomized intervention trials show
that vitamin A deficiency poses a significant problem in more than 70
countries.(14) Recent calculations suggest that roughly 150 million
children are deficient: every year 10 million children develop
xerophthalmia, 500,000 children are permanently blinded from xerophthalmia
and 1 to 2 million children die unnecessarily.(15)
Vitamin A deficiency disorders have not been quantified in women of
childbearing age. Older anecdotal reports(16, 17) and recent surveys(18,
19) indicate that night blindness from vitamin A deficiency is common
among pregnant women in India, Indonesia, Bangladesh, Nepal and elsewhere,
particularly during the latter half of pregnancy. Most surveys reveal
rates of night blindness of 10% or more during pregnancy in populations in
which the children are commonly deficient.(1) A recent large-scale
randomized placebo-controlled trial of vitamin A or beta-carotene
supplementation in Nepali women reduced maternal mortality by
approximately 40%,(20, 21) an effect that persisted for at least one year
Vitamin A deficiency disorder affects large numbers of young children and
women of childbearing age throughout the developing world. Current
estimates do not include China, where recent visits with nutritionists and
pediatricians in the southwestern regions identified cases of
xerophthalmia and where a recent UNICEF survey revealed depressed serum
retinol values and night blindness during pregnancy in large, impoverished
regions.(23-25) The size of the global problem is therefore likely to grow
as additional data are gathered.
Origins of Deficiency
Children begin life with an urgent need for vitamin A. Full-term infants ?
even those of well-nourished mothers in wealthy countries ? are born with
barely enough vitamin A to sustain them during the first few days of life.
During the first six months of life they need at least 125 mg of retinol
equivalents daily to prevent xerophthalmia and about 300 mg to thrive (and
accumulate adequate liver stores of 20 mg per gram of liver).(1, 26, 27)
The only significant source of vitamin A for young infants is breast milk
(or equivalent formulas). Except when mothers suffer from severe
protein-energy malnutrition, the quantity of breast milk is roughly
similar around the globe, but the concentration of vitamin A in that milk
varies dramatically with the vitamin A status of the mother.(26, 28) When
mothers are vitamin A deficient, breast milk concentrations will be low.
Without supplemental vitamin A, their infants will become deficient.
Children in developing countries are at risk of consuming a vitamin
A?deficient diet throughout life, not just during early infancy. Although
Western populations receive abundant preformed vitamin A from animal
products (eggs, butter, cheese, liver, processed foods fortified with
vitamin A), poor rural populations in developing countries rely on
beta-carotene, a precursor of vitamin A found in dark-green leafy
vegetables, carrots and colored fruits (mango and papaya). Even when
abundant, these are poor substitutes for animal sources of the preformed
vitamin: many children do not like dark-green leafy vegetables; fruits are
often costly, sold as a cash crop or highly seasonal (e.g., mangos); and
many vegetables bind beta-carotene tightly to their cellular matrices,
yielding little during digestion. Recent data indicate that the
bioavailability (and bioconversion) of dark-green leafy vegetable sources
of beta-carotene is much lower than previously supposed,(29, 30) with
perhaps no more than 2% to 4% being absorbed, converted to vitamin A, and
made available to meet metabolic needs.
Children in the developing world probably need more vitamin A than do
their better nourished Western counterparts. Diarrhea, childhood
exanthematous diseases and respiratory infections are more common in poor
rural populations, further reducing vitamin A absorption (diarrhea) while
increasing utilization (measles) and excretion (respiratory infection).
Why young children in developing countries are deficient in vitamin A is
clear. Their greatest risk of becoming vitamin A deficient is during the
first few years of life, when their diets are the least diverse, growth
(hence need) is greatest and they are at highest risk of life-threatening
infections. As they enter their school-age years these factors begin to
moderate even though deficiency persists and mild manifestations (e.g.,
night blindness and Bitot?s spots) remain common.
Why women are so frequently deficient is less clear. They also have a
similarly unvaried diet that is largely deficient in good sources of
preformed vitamin A. Pregnancy and lactation place additional burdens on
their meager vitamin A stores. Other consequences of pregnancy probably
explain why deficiency is most severe ? and night blindness most common ?
during the latter half of pregnancy. Even though pregnancy-related night
blindness spontaneously disappears during the early postpartum period, the
underlying deficiency does not. As a consequence these women suffer an
increase in mortality for at least one year postpartum.(20-22)
Combating Vitamin A Deficiency
There is global agreement on the need to combat vitamin A deficiency.(2,
14) More than 70 countries have formal intervention programs, although
only a few (Nepal, Indonesia, Tanzania, Bangladesh, Vietnam) have made
significant, discernible progress. Three basic strategies exist for
increasing vitamin A intake: increasing the consumption of foods rich in
vitamin A and provitamin A; fortifying commonly consumed dietary items
with vitamin A (or beta-carotene); and providing large, periodic, vitamin
A supplements to high-risk populations.
Many nutritionists consider increasing the consumption of natural dietary
sources of vitamin A to be the logical long-range solution to deficiency.
Despite occasional demonstration projects and correlational analyses,(31)
little definitive evidence exists that vitamin A sufficiency can be
achieved ? let alone sustained ? through traditional food sources,
particularly those available to poor, rural, high-risk populations. As
noted, vegetables are poor sources of provitamin A beta-carotene. Although
they contain considerable quantities of beta-carotene, these are not
readily bioavailable. It needs to be shown that vulnerable children can
consume quantities of dark-green leafy vegetables sufficient to normalize
their vitamin A status.
Adults may be able to obtain sufficient vitamin A by consuming far larger
amounts of vegetables and fruits than children consume or through the
greater diversity of their diet, but this too needs documentation. In at
least two studies, women provided daily with large helpings of dark-green
leafy vegetables failed to significantly improve their vitamin A
status(29, 32) in contrast to those fed cookies containing pure synthetic
(therefore readily absorbed) beta-carotene.(29) Introducing animal sources
of preformed vitamin A (e.g., eggs) into the diet might make a significant
difference but remains beyond the resources (and cultural patterns) of
many of the populations at highest risk.
Fortification by Conventional Means
Fortifying dietary items with preformed vitamin A or beta-carotene is a
proven strategy for preventing deficiency.(33) In the early 1900s Denmark
legislated vitamin A fortification of margarine because its growing dairy
exports deprived the poorer classes of once-abundant butter, for which
they initially substituted vegetable oil?based margarine, which is
naturally devoid of vitamin A. In the United States, Western Europe and
most wealthy countries, a wide variety of dietary items is fortified with
vitamin A (milk, margarine, cereal products). Developing countries have
experimented with fortifying a range of products with vitamin A
(monosodium glutamate, wheat, noodles, sugar). To date, only sugar
fortification, primarily in Latin America, has taken hold.(34)
Traditional fortification techniques require a dietary item that is
consumed in suitable quantities by the groups at highest risk; is
processed at a limited number of sites where the fortificant can be
conveniently added; stabilizes vitamin A during its normal shelf life in
the marketplace (vitamin A is unstable in salt, making salt unsuitable for
vitamin A but fine for delivering iodine); results in little increase in
cost to the consumer; and has acceptable organoleptic qualities (color,
smell, taste). These requirements have been difficult to achieve for
high-risk poor populations that generally consume a monotonous diet devoid
of expensive, centrally processed items.
Fortification by Genetic Modification
In an attempt to overcome some of the obstacles facing conventional
fortification, scientists have begun to genetically modify traditional
dietary items to produce beta-carotene. Monsanto produced rape seed and
mustard rich in beta-carotene and, more recently, scientists funded by the
Rockefeller Foundation produced a strain of rice ? golden rice ?
genetically modified to produce beta-carotene.(35) This may well herald an
important strategy for controlling vitamin A deficiency, particularly
because rice is the dietary staple of many of the most-deficient
Some hurdles need to be surmounted before golden rice or its variants can
have an effect. The strains must be able to grow under the varied
conditions in countries with vitamin A?deficient populations. The yield
and the cost must be attractive to the farmer (or benefit from public
sector subsidization). The organoleptic qualities of the rice must be
acceptable to the target population (women and children). The
beta-carotene needs to be bioavailable, the degree dependent on its
concentration in the rice, the matrices to which it is bound, the effect
of traditional cooking methods and the amount consumed.
Although genetically modified rice could go a long way toward controlling
vitamin A deficiency, it will never completely solve the problem. Many
deficient populations do not consume rice, and even within traditional
rice-consuming countries, some high-risk groups will not be able to afford
Vitamin A (retinol) supplements ? naturally occurring (as in cod liver
oil) or synthetically derived (multivitamin preparations) ? have long been
used to prevent vitamin A deficiency and its associated disorders.(2, 36)
Vitamin A is a component of prenatal and infant multivitamins routinely
consumed by Western populations. Periodic administration of large doses of
vitamin A to children was pioneered in India(37) and advanced globally
after the first major international meeting on the control of vitamin A
deficiency in 1974.(32)
Periodic supplementation is the most widely implemented intervention for
controlling vitamin A deficiency in the developing world. Countries have
found these programs to be relatively easy and quick to initiate at
relatively modest marginal cost.(2, 38) Supplements are extremely
inexpensive, at 2 to 4 cents per dose of 200,000 international units (IU).
Most of the cost is for the gelatin capsule; the cost for the vitamin A is
less than 1 cent.
The major cost for (and impediment to) population-wide supplementation is
the delivery system. Recommendations called for the administration of
200,000 IU every 4 to 6 months to all children 12 to 60 months of age.
Unfortunately, that often requires a delivery mechanism such as that
presently used successfully in a number of countries (e.g., Nepal and
Bangladesh). In Nepal, 37,000 village women volunteers reach more than 2
million children during special ?Vitamin A Days? held twice every year.(39)
To better use existing delivery channels, many countries have piggybacked
vitamin A distribution onto regular immunization efforts. In particular,
25,000 or 50,000 IU of vitamin A is given to young children at ages 6, 10,
and 14 weeks when they receive their diptheria, pertussis and tetanus
immunizations. A fourth dose (100,000 IU) is administered at age 9 months
with measles immunization.(40) The rationale for this schedule is that an
existing distribution mechanism is available, minimizing the marginal cost
of delivery; a high risk of deficiency exists during the first year of
life (200,000 IU is given to mothers 6 to 8 weeks postpartum to boost
breast milk vitamin A concentration); and infants are at greatest risk for
consequences of deficiency, particularly mortality. Coverage achieved by
supplement distribution programs has dramatically risen in the past two
years, largely because vitamin A administration was included in national
immunization days, which were designed to deliver polio vaccine. More than
40 countries reported covering more than 80% of their target children with
vitamin A supplements during 1998.(1, 41)
Although randomized controlled clinical trials have demonstrated the value
of periodic supplementation,(2) in practice it has proved difficult to
reach children after the first year of life; indeed, with immunization
rates falling below expected targets, these too have not met their goals.
To compound the problem, national immunization days will soon be phased
A recent multinational trial sponsored by the World Health Organization
(WHO) suggests that the present regimen of dosing mothers with 200,000 IU
postpartum and their children three times in the first 14 weeks of life
with 25,000 IU does not improve vitamin A status much beyond age 6
months.(42) In response, a recent informal consultation organized by WHO
recommended that doses to infants and mothers be increased: 400,000 IU to
postpartum women (in two doses during the preconceptual period) and 50,000
IU to infants at least three times before age 6 months. Although the
effect of these increases is yet to be ascertained, evidence suggests they
will be safe and effective.(27)
Undue concern over vitamin A toxicity, a rare and transient condition,(43)
has complicated the design of intervention strategies and unnecessarily
diverted attention and commitment from effective control strategies.
Because safety relates to the prevention of deficiency, only two issues
arise: teratogenicity and acute toxicity.
Very large doses of vitamin A during the first trimester of pregnancy can
be teratogenic, so high-dose supplementation of women of childbearing age
is only recommended during the infertile postpartum period.(40) Acute
toxicity, although harmless and transient, can result in nausea and
vomiting. If mothers notice and are concerned, it might result in lower
compliance rates, so supplement size is adjusted for the child?s age. Even
so, young children who might inadvertently receive multiples of the
recommended dose (in addition to increased amounts in breast milk) will
not suffer significant, permanent sequelae.(1) The implications for
intervention strategies are minimal.
Traditional foods cannot produce teratogenic or toxic effects. For
deficient populations the primary source of vitamin A is vegetables, which
lack the preformed vitamin. Ingesting large quantities of carrots and
other carotenoid-rich vegetables may produce high carotene levels, but
these are harmless. Because the body regulates conversion of beta-carotene
to vitamin A, serum retinol does not rise to toxic levels.
Programs that add retinyl palmitate (preformed vitamin A) to dietary items
carefully adjust the level of fortification to benefit consumers whose
diets are most deficient without exposing wealthier segments of
society, whose diets might be richer in preformed vitamin A, from
consuming excessive amounts. These programs take pains to achieve a
balance that best serves both groups. The choice of vehicle can optimize
Fortifying a product or a specific package of that product (e.g., the
smallest packets of monosodium glutamate) uniquely ingested by those who
are most deficient increases the amount of vitamin A that can be safely
added. Nonetheless, ongoing surveillance is valuable in identifying
isolated groups or individuals who purposely purchase and consume large
doses of supplements on a sustained basis.
Fortification through genetic modification poses no risks of vitamin A
toxicity. Genetically modified crops (e.g., golden rice, enriched canola
oil) produce beta-carotene, not preformed vitamin A.
This intervention is potentially the most problematic because it is
theoretically possible to overdose the recipient through frequent,
inadvertent dosing. From a practical standpoint, however, serious or
sustained side effects require very high, frequent and persistent dosing
(50,000 to 100,000 IU daily for 3 to 6 months).(1, 27, 40, 43) An often
expressed concern is that a child might receive three or even four
high-dose supplements within a month (a regular distribution, a dose
during measles, plus a third or fourth from an overly zealous local health
worker). The worst result, however, would be a day or two of nausea and
vomiting. This risk pales in comparison with the millions of children who
would otherwise die or be blinded.
A decade ago the public health and nutrition communities recognized the
need to improve the vitamin A status of young children throughout the
developing world.(44) The World Bank has estimated that vitamin A
supplementation (the only approach they modeled) was among the most
cost-effective health interventions available, at less than US$1 per
disability-adjusted life year.(45) Although more than 70 countries have
embraced the global goal of eliminating vitamin A deficiency as a public
health problem, progress has been slow, largely because of the costs and
logistical challenges to changing behavior (diets), delivering large-dose
supplements regularly, and fortifying traditional dietary items. A number
of bilateral and international agencies recently recommitted themselves to
these efforts, even as continuing research expands the implications of
deficiency. New tools, such as genetically modified staple crops, could
provide important strategies and stimulate these global efforts.
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