2, June 2000
Welcome to the second issue of the Novartis Foundation's
e-mail Bulletin. This issue features reports on
(Advancing rice research with
cutting edge science
Symposium 236 27-29 March 2000)
First, some statistics. As a staple
food providing roughly one-quarter of the calorie intake of human
populations, rice is undoubtedly one of the most important food crops
of the world. And the staggering fact is that in many parts of Asia,
rice contributes as much as three-quarters of the food intake. During
the Green Revolution, between 1970 and 1985, rice production grew at a
faster rate than the human population; an enormous achievement brought
about by advances in agricultural science. However, since the
mid-1980s, rice production has lagged behind population growth, and
estimates are that rice harvests will have to increase by some 40 per
cent over the next 20 years to meet the increased demand -- the 'yield
gap'. Given that there is limited rice production capacity outside
Asia, and that many countries in South Asia do not have the resources
to buy rice from exporting countries, it becomes clear that the only
way to meet this goal is to raise rice yields in rice-producing
countries. It is against this background that this symposium was held,
at the International Rice Research Institute (IRRI) in the
Philippines. IRRI is to rice research what Lord’s is to cricket.
With a track record of 40 years of pioneering rice research and a
concentration of expert rice scientists, it was the perfect place to
hold a meeting that brought together some of the leading researchers
in the field to discuss ways in which this yield gap may be bridged.
There is insufficient space here to do
justice to all the high quality research that was discussed at the
symposium -- I will just focus on a few of the topics that were
discussed. Many people will already be aware of the pioneering studies
presented by Peter Beyer on the development of 'golden' rice. This is
rice that has enhanced vitamin A content, through transformation with
two daffodil genes, resulting in yellow grains. This rice, if made
widely available, could help the millions of children in Asia
suffering from preventable blindness.
Maurice Ku's work on trying to engineer
the more efficient C4 photosynthetic pathway into the less efficient
C3 rice plant has also attracted a lot of press interest in recent
months. Maurice described some of the impressive progress that his
laboratory has made using transgenic technology, but the discussion
revealed that there are still some severe obstacles to be
Kazuko Yamaguchi-Shinozaki described
studies showing that in the model plant Arabidopsis, salinity,
cold and drought tolerance can be enhanced by transformation with a
series of transcription factors, work which holds obvious promise for
rice if rice homologues of these genes can be identified. One way to
increase yields is by addressing the factors that cause crop losses,
such as disease. Along these lines interesting work was presented at
the symposium by Jane Parker, Xinnian Dong and Jan Leach, who have
been investigating the genetics of defence pathways.
Finally, one topical issue that was
raised at the meeting concerned the worrying attitudes of the public
towards agricultural biotechnology, and in particular towards
genetically modified foodstuffs. There was no doubt in the minds of
the researchers at the symposium that in order to avoid starvation in
Asia, the development of transformed (genetically modified) crops is
going to be essential in order to bridge the yield gaps. It is a
tragedy that the application of some of the groundbreaking and elegant
science presented at the symposium may be jeopardized by public
sentiment in western nations, who do not suffer food shortages.
‘Rice biotechnology: improving
yield, stress tolerance and grain quality’ will be published by
Wiley in 2001.
For abstracts from the symposium see http://www.novartisfound.org.uk/fp236.htm
AGEing – breaking the
(Ageing vulnerability Symposium 235
29 February-2 March 2000)
For all the claims of anti-ageing
creams and therapies, nothing has so far restored the vigour of youth
or even delayed the inevitable process of growing old. But, as was
discussed at this recent symposium, research scientists have now
developed a drug that may rejuvenate hearts and muscles by breaking
the stiff bonds between sugars and proteins that are involved in
Anthony Cerami (New York, USA) first
suspected sugar may have an impact on ageing when he began his
research in diabetes. As diabetics age more rapidly, excess sugar in
blood seemed the likely culprit. Although the sugar in our diet
provides us with a ready source of energy, in the body, glucose
becomes highly reactive. Acting as molecular glue, sugars attach
themselves to the amino groups in tissue proteins to form yellow-brown
compounds known as advanced glycation endproducts (AGEs).
Inevitably, with continued glucose
consumption, AGEs slowly accumulate, turning our tissues yellow and
leathery. Piling on yellow-brown pigment in the teeth, bones and skin
is mostly harmless. But long-lived structural proteins, such as
collagen and elastin stiffen irreversibly. The result is a
constellation of body changes -- thickened arteries, stiff joints,
feeble muscles, failing kidneys and lungs -- the hallmarks of old age.
In diabetic patients, as a result of high blood sugar, AGEs accumulate
faster. Indeed, there are similar amounts of AGEs in collagen from
elderly people and diabetics.
Cerami’s quest has been to find a
compound to tie up excess glucose and thus slow down premature ageing.
The food industry provided him with an unexpected source of
inspiration. Since 1912, food chemists have known that extreme heat
such as an oven, forms tight chemical bonds between sugars and
proteins -- the same reaction as takes place inside the body when AGEs
form. This Maillard reaction turns roasted turkey, toast, and coffee
beans golden brown. Crucially, food
chemists also knew that chemical inhibitors would prevent browning,
keeping food and beverages looking fresh.
Profiting from this knowledge, Cerami’s
team has come up with drugs he calls ‘breakers’, which can undo
the crosslinking once it has already taken place. The ‘breaker’,
phenacylthiazolium chloride, ALT-711, has been designed to shatter
protein crosslink bonds, thus attenuating the pathological conditions
that accompany AGEs. Diabetic animals, old dogs and elderly rhesus
monkeys given the compound daily for three weeks yielded spectacular
results. ‘The heart and major arteries which were quite stiff become
more pliable and elastic, so the heart can pump more blood -- similar
to what you’d see in a young animal.’
Cerami envisages multiple uses for
breakers in pathologies that involve stiff tissues. For example, in
glaucoma, to increase the elasticity of the draining canal and prevent
the build up of pressure, to halt the decline in lung function that
occurs with age, to make the prostate more pliable in ageing men, when
it enlarges and stiffens, and even to treat ageing skin. Although he
warns that it will be at least 10 years until such drugs, currently
undergoing clinical trials, are approved for use in humans.
The full version of this article is
published in the July 2000 issue of Scientific American.
‘Ageing vulnerability’ will be
published by Wiley in December 2000.
For abstracts from the symposium see http://www.novartisfound.org.uk/fp235.htm
(Gastroenteritis viruses Symposium
238 16-18 May 2000)
Will poorer nations accept a
life-saving vaccine that has been deemed unsafe in the USA? In rich
countries, diarrhoea is not a killer. But in developing countries,
diarrhoea is often a death sentence, especially for young children.
The toll is huge: severe gastroenteritis is responsible for a quarter
of all deaths worldwide. Rotaviruses are the main agents behind
life-threatening gastroenteritis, causing an estimated 45 per cent of
severe diarrhoea worldwide.
Water and food contaminated with faeces
are the vehicles for these ubiquitous viruses. Even the
hygiene-conscious West with the luxury of a clean water supply has
been unable to eradicate the lurking threat of gastroenteritis. But
the yawning gap in health provision between rich and poor nations
becomes painfully obvious in diarrhoeal infections. In rich countries,
severe diarrhoea is kept in check by prompt and effective treatment.
Whereas in poorer nations, therapy is often too late or difficult to
deliver, making vaccination the only feasible option.
A vaccine for rotavirus, RotaShield®,
already exists. Unfortunately, it has fallen into an ethical minefield
that threatens to keep it away from those who will benefit the most.
Albert Kapikian (National Institutes of Health, USA) developed a
vaccine that protects against the four most common types of strains.
In 1998, after exhaustive trials, the vaccine was licensed by the US
Food and Drug Administration. A year later, after tens of thousands of
immunizations, the vaccine was withdrawn, when 15 young children were
hospitalized for intussusception (a
blockage in the bowels caused by the intestine folding over itself).
The task at hand is to ascertain
whether the link is real. The odds of developing intussusception
without vaccination have never been defined, Kapikian told researchers
at the symposium. If the vaccine is finally cleared (the data should
be ready by October 2000), it is still unlikely that Americans and
Europeans will take kindly to it. In these countries, even the
severest forms of diarrhoea are easily treated, so it may be a
struggle to persuade mothers to inoculate their children with a
vaccine that could prove deadly -- however minute the risk.
Things are quite different in the poor
countries of sub-Saharan Africa, Asia and South America. Every day,
rotavirus kills 2000 infants, and the vaccine could cut deaths
dramatically. For them, the balance is tipped: the vaccine’s
benefits clearly outweigh the risks. The issue puts leaders of
developing nations in a precarious position. On the one hand, why
accept a vaccine that has been deemed unsafe and withdrawn from the US
market. On the other, failing to improve matters for their people when
a solution is at hand almost borders on the immoral. Unfortunately,
the vaccine has made a false start, and at the moment, the chances of
seeing it reversed seem depressingly remote.
‘Gastroenteritis viruses’ will
be published by Wiley in 2001.
For abstracts from the symposium see http://www.novartisfound.org.uk/fp238.htm
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