The potential impact of plant biotechnology on the Millennium Development Goals.

Abstract

The eight Millennium Development Goals (MDGs) are international development targets for the year 2015 that aim to achieve relative improvements in the standards of health, socioeconomic status and education in the world's poorest countries. Many of the challenges addressed by the MDGs reflect the direct or indirect consequences of subsistence agriculture in the developing world, and hence, plant biotechnology has an important role to play in helping to achieve MDG targets. In this opinion article, we discuss each of the MDGs in turn, provide examples to show how plant biotechnology may be able to accelerate progress towards the stated MDG objectives, and offer our opinion on the likelihood of such technology being implemented. In combination with other strategies, plant biotechnology can make a contribution towards sustainable development in the future although the extent to which progress can be made in today's political climate depends on how we deal with current barriers to adoption.

Full text

Page 1

OPINION PAPER
The potential impact of plant biotechnology on the Millennium
Development Goals
Dawei Yuan•Ludovic Bassie•Maite Sabalza•Bruna Miralpeix•
Svetlana Dashevskaya•Gemma Farre•Sol M. Rivera•Raviraj Banakar•
Chao Bai•Georgina Sanahuja•Gemma Arjo ´ •Eva Avilla•Uxue Zorrilla-Lo ´pez•
Nerea Ugidos-Damboriena•Alberto Lo ´pez•David Almacellas•Changfu Zhu•
Teresa Capell•Gunther Hahne•Richard M. Twyman•Paul Christou
Received: 3 November 2010/Revised: 18 December 2010/Accepted: 18 December 2010
? Springer-Verlag 2011
Abstract
(MDGs) are international development targets for the year
2015 that aim to achieve relative improvements in the
standards of health, socioeconomic status and education in
the world’s poorest countries. Many of the challenges
addressed by the MDGs reflect the direct or indirect con-
sequences of subsistence agriculture in the developing
The eight Millennium Development Goals
world, and hence, plant biotechnology has an important
role to play in helping to achieve MDG targets. In this
opinion article, we discuss each of the MDGs in turn,
provide examples to show how plant biotechnology may be
able to accelerate progress towards the stated MDG
objectives, and offer our opinion on the likelihood of such
technology being implemented. In combination with other
strategies, plant biotechnology can make a contribution
towards sustainable development in the future although the
extent to which progress can be made in today’s political
climate depends on how we deal with current barriers to
adoption.
Keywords
Development Goals ? Poverty ? Hunger ? Malnutrition ?
HIV/AIDS ? Agriculture ? Developing countries
Plant biotechnology ? Millennium
Introduction
The Millennium Development Goals (MDGs) are a set of
eight ambitious international development targets for the
year 2015, which were agreed by 192 members of the
United Nations as well as numerous non-governmental
organizations (NGOs) at the Millennium Summit in 2000
(Appendix 1). The aim of the MDGs is to improve stan-
dards of health, socioeconomic status and education by
tackling poverty, hunger and disease, increasing educa-
tional opportunities and creating a global development
partnership (UN 2010a).
We are now more than two-thirds of the way through the
program, and progress towards the goals has been patchy,
with significant improvements in the rising economies such
as China and India, but little progress in some other
countries, particularly in sub-Saharan Africa (UN 2010b).
Communicated by R. Reski.
A contribution to the Special Issue: Plant Biotechnology in Support of
the Millennium Development Goals.
D. Yuan ? L. Bassie ? M. Sabalza ? B. Miralpeix ?
S. Dashevskaya ? G. Farre ? R. Banakar ? C. Bai ?
G. Sanahuja ? G. Arjo ´ ? E. Avilla ? U. Zorrilla-Lo ´pez ?
N. Ugidos-Damboriena ? A. Lo ´pez ? D. Almacellas ?
C. Zhu ? T. Capell ? P. Christou (&)
Department of Plant Production and Forestry Science,
ETSEA, University of Lleida, Av. Alcalde Rovira Roure,
191, 25198 Lleida, Spain
e-mail: christou@pvcf.udl.es
S. M. Rivera
Chemistry Department, ETSEA, University of Lleida,
25198 Lleida, Spain
G. Arjo ´
Department of Medicine, University of Lleida, Lleida, Spain
G. Hahne
De ´partement Soutien Formation, IRD, 44 Boulevard de
Dunkerque, CS 90009, 13572 Marseille Cedex 02, France
R. M. Twyman
Department of Biological Sciences, University of Warwick,
Coventry CV4 7AL, UK
P. Christou
Institucio ´ Catalana de Reserca i Estudis Avanc ¸ats, Passeig Lluı ´s
Companys 23, 08010 Barcelona, Spain
123
Plant Cell Rep
DOI 10.1007/s00299-010-0987-5

Page 2

China has almost halved its poverty-stricken population
over the last decade and is well on the way to realizing all
the MDGs by 2015. In contrast, the major target countries
in sub-Saharan Africa have reduced the level of poverty by
less than 1% and seem unlikely to meet any of the MDGs
(UN 2010b).
The success of China and India has much to do with
their economic growth, but growth is not a prerequisite for
the achievement of MDG targets. Bangladesh, for example,
has shown that progress can be made with little or no
growth simply by adopting and rolling out inexpensive
solutions on a large scale, including national vaccination
campaigns and nutritional supplementation programs
(UNICEF 2010). Tying the MDGs to expensive solutions
that in turn depend on either economic growth or donations
in aid cannot be maintained indefinitely, and it is therefore
imperative that inexpensive but scalable solutions are
deployed as rapidly as possible to provide a sustainable
basis for development. In this context, plant biotechnology
has a role to play by providing healthier and more nutri-
tious crops and also new platforms to produce inexpensive
vaccines and drugs. However, the impact of plant bio-
technology is not limited to augmenting or replacing
expensive intervention programs. Biotechnology can create
plants that reduce the impact of weeds, insect pests, dis-
eases and harsh environments, providing a basis not only
for the reduction of hunger through more successful sub-
sistence agriculture but also the stimulation of economic
prosperity by providing higher yields of better quality
crops that increase the wealth as well as the health and
wellbeing of poor agricultural workers. Although plant
biotechnology is not a panacea for the world’s socioeco-
nomic woes, it is already being used in numerous ways to
address the Millennium Development Goals. There remain
significant barriers to adoption that are largely political in
character, with little or no rational scientific basis. Over-
coming these political hurdles in the short term is a more
challenging objective than achieving technological pro-
gress (Farre et al. 2009).
MDG1: Eradicate extreme poverty and hunger
Overview
The number of people living in hunger currently oscillates
around one billion, which represents nearly one in every
seven people in the world (FAO 2009b). Hunger can be
defined as an insufficient daily intake of energy (the average
requirement being 2,000 kcal per day), and the figure of one
billion therefore excludes those who receive sufficient cal-
ories but are nevertheless malnourished due to the absence
of essential vitamins and minerals (we return to this topic
later). The hungry has limited access to food but not
because of insufficient production. Indeed, there is plenty of
food, enough to support a much higher global population
than exists today, but there is inadequate food distribution,
and the world’s poorest people cannot afford to purchase the
food that is available. Hunger, at least at present, is there-
fore caused by poverty and poor distribution rather than
insufficient global production (DFID 2010).
The World Bank defines extreme poverty as living on
less than US $1.25 per day. MDG1 is therefore expressed in
the form of three objectives, the first to reduce the number
of people living in poverty by 50%, the second to improve
employment opportunities (particularly for women and
young people) and the third to reduce the level of hunger
(Fig. 1). These are interlinked objectives, and they need to
be tackled simultaneously to see improvements in all the
three. Progress towards MDG1 is also important to ensure
progress towards most of the other MDGs, particularly
those that aim to reduce the burden of disease and improve
education. Poverty and hunger both lead to poor health and
loss of opportunity, creating a vicious cycle in which people
are forced to endure a monotonous existence that focuses
solely on survival (Islam 2008).
Although urban poverty is a growing problem, most of
the world’s poorest people are rural dwellers and depend on
subsistence agriculture (Fan et al. 2005). Strategies to
address extreme poverty in rural areas should therefore
focus on improving agricultural productivity to allow the
poortoproduceenoughfoodtosurvive, theremainder being
marketed and generating income. Short-term solutions such
as providing food aid will not provide long-term and sus-
tainable progress towards MDG1. Instead, there needs to be
a drastic shift in socioeconomic policy focusing on agri-
cultural and commercial development, with modern seed
varieties playing an important role because they generate
the most vigorous crops (Sanchez 2009). Most subsistence
calories are obtained from cereal crops, particularly rice and
maize. These two crops are the staple diet of more than 75%
of the human population (FAO 2009a). Maize also provides
much of the fodder for livestock in the countries where it is
grown, including both developed countries such as the US,
and many countries in Africa. The short-term objective
should therefore be to reduce the yield gap in cereal crops
(the gap between potential yields and actual yields) to
reduce hunger, improve health and create economic pros-
perity. In the longer term, it will be necessary to apply the
samesolutionstodiversefruitandvegetablecropsaswellas
cash crops such as cotton, tobacco and coffee.
The role of plant biotechnology
Plant biotechnology can help to achieve MDG1 through the
deploymentofhigh-yielding genetically engineered
Plant Cell Rep
123

Page 3

varieties that are resistant to weeds, insect pests and dis-
eases caused by viruses, bacteria and fungi, and that are able
to withstand harsh environmental constraints such as
drought (Farre et al. 2009). Weeds, insect pests and
pathogens can reduce yields either by adversely affecting
plant growth and development, or by consuming and/or
spoiling the products of food crops in the field or in storage.
Globally, this reduces crop yields by up to 30%, but the
impact in developing countries can be much higher because
the climatic conditions favor the survival and breeding of
insect pests and disease vectors. After pests and diseases,
unfavorable environmental conditions such as drought, poor
soil quality and (in Asia) flooding also have a devastating
effect. The development of crops with an inbuilt capacity to
withstand these effects could help to stabilize crop pro-
duction and hence significantly contribute to food security
and economic prosperity (Christou and Twyman 2004).
Weeds
Weed management is the largest single input into agri-
culture in both industrialized and developing countries.
However, whereas weed management in the developed
world is highly mechanized and has benefited extensively
from the technological advantages provided by genetically
engineered herbicide-resistant crops and broad-spectrum
herbicides, developing country agriculture currently relies
on an army of laborers, mostly women, who tend the land
and spend long hours removing weeds manually (Akob-
undu 1991).
Two issues compound the impact of weeds in developing
countries—the lack of resources to adopt technological
solutions that are taken for granted in the developed world,
and the disinterest shown by research organizations in the
west to tackle weed species that are specific to Africa and
Asia (Gressel et al. 2004). In Africa, maize and sorghum
crops are often infested by Striga, a genus of parasitic
flowering plants that is very difficult to control once
established because it builds up a resilient seed bank in the
soil (Parker 2009). Striga represents such a severe constraint
to maize production that controlling this weed is seen as the
key to resolving Africa’s dependence on subsistence agri-
culture (Hearne 2009). There has been some recent success
in the conventional breeding of resistant sorghum varieties
by combining traits that make the sorghum plants poor
inducers of Striga germination and poor hosts for coloni-
zation (Ejeta et al. 2007), but it has not been possible to
achieve the same goals in maize. Progress towards the
selective control of Striga in maize has been made through
mutation and conventional breeding for imazapyr resistance
(Kanampiu et al. 2002), which has been implemented as
StrigAway technology co-developed by CIMMYT, BASF
and the Weizmann Institute (Mataruka et al. 2010).
Although this requires the application of herbicides, it is not
necessary for farmers to spray their crops because the her-
bicide can be applied directly to the seed. A complementary
biotechnology solution is to introduce herbicide resistance
directly into maize. Glyphosate-resistant transgenic maize
has been adopted in South Africa, which allows one worker
with a backpack sprayer to control weeds over several
CIS Europe
Developing regions
Western Asia
Northern Africa
Transition countries of South-Eastern Europe
CISAsia
South-Eastern Asia
Eastern Asia
Latin America/Caribbean
2005
1990
2015 target
Sub-Saharan Africa
Southern Asia
Souther Asia excluding India
0 10203040 5060
70
Fig. 1 Proportion of people
living on less than US $1.25/day
by region, 1990 and 2005,
compared to 2015 MDG targets.
Source: UN (2010a)
Plant Cell Rep
123

Page 4

hectares. Although South Africa does not suffer from Striga
infestations to the same extent as other countries in the
region, the use of glyphosate resistance for general weed
control shows that it could also be applied to tackle Striga
infestations (Gressel and Valverde 2009).
The industrialization of rice cultivation in Asia has also
generated an emerging problem with weeds. The switch
from transplanting rice plantlets into flooded paddies (weed
control by water) to direct seeding (weed control by her-
bicides) has led to the emergence of herbicide-resistant
Echinochloa species that were formerly quite easy to
control with selective herbicides (Valverde and Itoh 2001)
and feral rice species (Valverde 2005). Here, transgenic
strategies need to be applied with care because of the rapid
evolution of herbicide resistance that has already been
documented, and the likelihood that transgenes conferring
herbicide resistance could introgress into weedy rice spe-
cies and eliminate the selective difference between weedy
and cultivated rice (Gealy 2005).
Insect pests, insect-borne diseases
and the consequences of pest infestations
Many of our crop plants are attacked by insect pests, and
devastating losses occur throughout the world due to pest
infestations either in the field or in stored products. In the
developing world, about half of all crop production is
thought to be lost to insects, 15% of these losses occurring
due to post-harvest consumption and spoilage (Christou
et al. 2006). Insects not only cause direct yield losses by
damaging and consuming plants but also act as vectors for
many viral diseases, and the damage they inflict encourages
bacterial and fungal infections, the latter resulting in con-
tamination with mycotoxins.
A good example of the positive impact of plant bio-
technology is the development of pest-resistant crops
expressing insecticidal toxin genes from the soil bacterium
Bacillus thuringiensis (Bt). Different strains of Bt produce
different toxins which are both potent and highly specific
against narrow taxonomic groups of insects, making them
harmless to mammals and to beneficial insects (Sanahuja
et al. 2011). In developing countries, Bt crops have been
extraordinarily successful and beneficial, increasing yields,
reducing the use of pesticides and the fuel needed for
spraying, and improving the economic status of farmers
while at the same time preserving biodiversity (James
2010; Brookes and Barfoot 2010).
The adoption of Bt crops in India provides strong sup-
port for the role of plant biotechnology in progress towards
MDG1. In 2009, more than 5.5 million small-scale farmers
planted a total of 8.4 million hectares of Bt cotton, repre-
senting nearly 90% of the national total (James 2010).
More than half of these crops contained multiple Bt genes
providing resistance against different pests, and for the first
time locally developed varieties were planted instead of
varieties developed in the US, therefore keeping all the
agricultural profits within India’s economy rather than
servicing foreign royalty payments. India is now the
world’s largest cotton exporter (having been a net importer
at the beginning of the decade), and it is estimated that
rural farmers have benefitted from the technology through
yield improvements to a total amount exceeding US $5
billion. Net yields per hectare have doubled in 10 years
while agrochemical inputs have halved (APCoAB 2006;
Manjunath 2008). The widespread adoption of Bt cotton in
India has also helped to address the concerns of critics, who
highlight the potential for resistant pests to evolve under
intense selection pressure. Against these expectations, the
first generation of Bt crops has maintained efficacy against
nearly all targeted pest populations for more than a decade
(Bourguet 2004). The scarcity of resistant populations
despite the lack of integrated pest management suggests
that resistance may attract a fitness penalty in the absence
of the Bt toxins (Sanchis and Bourguet 2008). Resistant
populations have appeared for a small number of pests,
such as pink bollworm (Pectinophora gossypiella) which
has evolved resistance to Bollgard I cotton (expressing the
Cry1Ac toxin) in the Amreli, Bhavnagar, Junagarh and
Rajkot areas of Gujarat. Resistance is anticipated because
each toxin binds to a specific receptor in the brush border
of midgut epithelial cells, and point mutations affecting
toxin/receptor interactions would be strongly favored under
selection. However, no resistance has been observed in
fields growing the Bollgard II variety, which expresses the
Cry1Ac and Cry2Ab toxins simultaneously (Monsanto
2010). These toxins bind different receptors, and the like-
lihood of mutations occurring in genes for both receptors is
much lower than the likelihood of a single mutation, so this
strategy of ‘pyramiding’ resistance genes (i.e. expressing
multiple toxins with different targets in the pest) is a very
powerful approach to prevent the evolution of resistant pest
populations.
In the last year, Indian regulatory authorities also
approved Bt brinjal (eggplant), India’s first biotechnology-
derived major food crop. Eggplant is a profitable crop but
is extremely susceptible to pests, which cause up to 70%
yield losses. Pest control normally requires repeated gen-
erous pesticide applications, up to 40 applications in
120 days, which many farmers cannot afford resulting in
less intense treatments that are ineffective (Jayaraman
2010). The Bt variety has the potential to increase net
yields by 33% while reducing pesticide use by up to 80%,
thus lifting another 1.4 million farmers out of poverty
(James 2010), but the regulatory approval was overruled by
the government after lobbying by activists, and Bt brinjal is
now subject to an indefinite moratorium pending additional
Plant Cell Rep
123

Page 5

safety data (Balga 2010). The technology behind Bt egg-
plant was freely donated by Maharashtra Hybrid Seeds
Company Ltd. (MAHYCO), who co-developed the product
with Monsanto, to public sector institutions in India,
Bangladesh and the Philippines for use by small resource-
poor farmers, with 18 varieties awaiting final approval.
These farmers will now be deprived of an opportunity to
increase their economic prosperity for the foreseeable
future (Jayaraman 2010).
As well as the direct impact of insect pestson crop yields,
insects also act as vectors for viruses and fungal spores,
encouraging crop diseases and fungal colonization of stored
grains.OneoftheindirectbenefitsofBttechnologyhasbeen
to reduce the level of mycotoxin contamination in grains
such as maize by reducing damage and spore transmission
(Brookes 2008; Wu 2007). Mycotoxins such as aflatoxin,
deoxynivalenol, fumonisin and zearalenone are the sec-
ondary metabolites produced by fungi that act as anti-
nutritional factors when present at low doses in food,
therefore preventing humans gaining the full benefit of the
calories they consume (Wu 2007). Mycotoxins also affect
domestic animals (Miller and Marasas 2002), so they have a
compound impact on food security by limiting weight gain
in farm animals as well as directly affecting humans. The
consumption of mycotoxins also carries a disease burden
because they are carcinogenic and can also suppress the
immune system, e.g. fumonisin has been revealed as an
exacerbating factor in susceptibility to HIV (Williams et al.
2010). It is therefore important to realize that poor nutrition
and disease can have a synergic effect on the welfare of the
world’s poorest people, particularly the combination of
limited calories, mycotoxin-contaminated grain, HIV and
otherdiseasesinsub-SaharanAfrica,wheremaizeisastaple
crop. Bt maize shows a consistently lower level of myco-
toxin contamination and can therefore help to address this
compound effect. There is also evidence that the lower
levels of mycotoxin contamination specifically attract a
price premium in some developing countries, providing
anotherimpetustoliftfarmersoutofpoverty(Yorobe2004).
Drought
Agriculture is highly dependent on water, and therefore,
access to fresh water is as important for agricultural pro-
ductivity as the quality of the seeds and the soil. With fresh
water resources dwindling, the impact of drought can be
devastating on crops, and the use of biotechnology to
develop varieties that require less water and that are tol-
erant to drought conditions is now becoming as important
as pest and disease resistance.
Drought stress in crops induces a number of response
pathways including protection against reactive oxygen
species, the active export of sodium ions and the synthesis
of small molecules called osmoprotectants that increase the
osmotic potential of cells causing them to retain water.
Efforts focusing on direct responses such as the introduction
of transgenes encoding antioxidant enzymes, enzymes that
synthesize antioxidant compounds, genes encoding sodium
transporters, and enzymes that synthesize osmoprotectants
have resulted in many laboratory strains of transgenic plants
that survive in concentrated salt solutions (Bhatnagar-
Mathur et al. 2008). Other researchers have targeted the
genes that regulate stress pathways (receptors, intracellular
signaling molecules and transcription factors) which may
be more useful because they, in turn, regulate a large
number of protective genes (Bhatnagar-Mathur et al. 2008).
A drought-tolerant variety of maize co-developed by
Monsanto and BASF is to be launched in the US in 2012
(James 2010). This expresses a stress-responsive tran-
scriptional regulator that increases yields by up to 35%
under water limiting conditions (Nelson et al. 2007).
Stress-responsive transcription factors are one of three key
classes of regulators that have been used to develop
drought-tolerant varieties, the others being proteins that
control signaling and post-translational modification in
stress pathways, and regulators of osmoprotectant synthesis
and metabolism such as the Bacillus subtilis chaperone
CspB which is expressed in another drought-tolerant vari-
ety developed by Monsanto (Castiglioni et al. 2008).
Although Texas in the US suffered its worst drought for
50 years in 2009 (with estimated losses of US $3.5 billion,
approximately one-sixth of the agriculture market value),
the situation in Africa and parts of Asia is much worse,
with regular harvest failures due to insufficient rainfall and
the absence of an irrigation infrastructure. Monsanto is part
of WEMA (Water Efficient Maize program for Africa)
which also includes the Gates Foundation, the Howard
Buffet Foundation, CIMMYT and several stakeholders in
sub-Saharan Africa, and it is committed to donating a
royalty-free drought-tolerant maize variety for humanitar-
ian use by 2017 (Mataruka et al. 2010). Under moderate
drought conditions in Africa the yield expected from the
tolerant variety should provide an additional 12 million
tons of maize, providing food for over 20 million people
who would otherwise depend on food given in aid.
MDG2 and MDG3: Achieve universal primary
education, promote gender equality
and empower women
Overview
Many developing countries are close to providing universal
primary education, with the total number of primary-age
children not attending school falling from 115 million in
Plant Cell Rep
123

Page 6

2002 to 72 million in 2007, even with growing populations.
Again, however, the picture is less encouraging in sub-
Saharan Africa and South Asia, with 41 and 31.5 million
primary-age children out of school, respectively (UN
2010a). In all developing regions, children in rural areas
are twice as likely to be out of school as children living in
urban areas, and children with disabilities and special needs
are the least likely of all to receive a school education
(Fig. 2a).
The underlying reasons for the trends discussed above
reflect the direct costs of sending children to school, as well
as the impact of losing potential workers on family farms.
Achieving universal education therefore requires a shift in
attitudes as well as the provision of educational opportu-
nities, and also requires that children are healthy, ade-
quately fed and well nourished. Abolishing school fees and
subsidizing costs (e.g. for textbooks, uniforms and trans-
portation) will make primary education more affordable for
parents. Programs that link education, health and nutrition,
such as school meal programs and social protection mea-
sures are necessary to achieve these aims, ultimately
leading back to effective governance (Sachs and McArthur
2005). It is also important to encourage parental involve-
ment in achieving MDG2.
Girls are less likely to be educated than boys throughout
the developing world, and the prevailing culture is male
dominated, a trend exacerbated in rural areas (Fig. 2b, c).
Therefore, the level of illiteracy is higher in women; they
are less likely to be employed; they tend to fill low-paid
positions if they are employed and are often excluded from
positions of authority (UN 2010a). Women overall suffer
more from poverty and are often completely dependent on
men financially. Furthermore, women are more likely to
suffer from poor health and malnutrition, and more women
than men in developing countries are HIV positive
(UNAIDS 2008).
As with MDG2, a change of attitude is important to
achieve MDG3, focusing on the rights of women to play an
equal role to men in society. Overlapping with MDG2, one
of the objectives of MDG3 is to strengthen opportunities
for the education of girls and women, while meeting the
above-mentioned commitments to universal primary edu-
cation. Other objectives are to guarantee women’s sexual
and reproductive health rights, their property and inheri-
tance rights, and their access to infrastructure, strive for
gender equality in employment, increase women’s influ-
ence in local and national governance, and combat
domestic violence.
The role of plant biotechnology
Plant biotechnology cannot directly contribute to progress
in either MDG2 or MDG3, but it can help by making
numerous indirect impacts to improve health, wealth and
wellbeing, and by providing educational opportunities. The
role of plant biotechnology in the achievement of MDG1 as
discussed above is pertinent because this reduces hunger
and poverty. Many children from rural communities do not
attend school because their parents cannot afford to send
them, but increasing the wealth-generating potential of rural
farmers by providing them with better crops is one way to
30
35
5
10
15
20
25
Girls
Boys
0
UrbanRural
30
30
35
15
20
25
Girls
Boys
0
5
10
Wealthiest 40% Poorest 60%
Primary school age
Percentage of school non-attendance
40
50
60
10
20
30
Girls
Boys
0
Wealthiest 40%Poorest 60%
Secondary school age
Fig. 2 Percentage of out-of-school children by gender, in 42
countries, up to 2008. a All children, by area of residence (rural or
urban). b Primary-age children, by household wealth. c Secondary-
age children, by household wealth. Source: UN (2010a)
Plant Cell Rep
123

Page 7

increase the proportion of children going to school. Fur-
thermore, transgenic crops make tillage, pesticide spraying
and weeding unnecessary and release women and children
who would otherwise be forced to work on the land,
allowing them the opportunity for education (Gressel 2009).
It is often women that carry out the laborious agricultural
work such as soil preparation, planting, weeding and har-
vesting, either for subsistence farming (as unpaid family
workers) or as a service without financial security or social
benefits, so the reduction in labor requirements has a dis-
proportionately positive impact on women and girls,
simultaneously addressing MDGs 2 and 3.
The widespread adoption of Bt cotton in India is one of
the primary reasons for the dramatic increase in school
attendance by primary-age children over the last decade,
but its impact on girls and women has been even more
remarkable (Subramanian et al. 2010; Subramaniam and
Qaim 2010). Comparing Bt and conventional cotton, the
average wage per hectare increased by US $40, with
women experiencing a greater income gain (55% average),
equivalent to 424 million additional days of employment
for women (Fig. 3). The potential role of plant biotech-
nology in reducing the nutritional and health burden on
women is discussed under MDGs 4 and 5 below.
MDGs 4 and 5: Reduce child mortality and improve
maternal health
Overview
Nearly 9 million children under the age of 5 years die
every year, 40% during their first month of life, and most of
these deaths are concentrated in the world’s poorest
countries in sub-Saharan Africa and South Asia (UN
2010a). The deaths are predominantly caused by diseases
that could be prevented or treated, and the mortality rate is
exacerbated by poor maternal health usually reflecting
underlying chronic malnutrition. MDG4 aspires to reduce
the infant mortality rate in developing countries by two-
thirds based on the number of deaths before the age of
5 years per 1,000 live births, specifically targeting the
number of deaths before first birthday and specifically
mentioning the fight against measles (Fig. 4).
The causes of infant mortality are diverse, but the
leading factors are pneumonia, diarrhea, malaria and HIV/
AIDS, which together accounted for 43% of all infant
deaths worldwide in 2008. We defer the discussion of HIV/
AIDS and malaria to MDG6, which specifically focuses on
those diseases. Pneumonia and diarrhea together account
for a third of all under-five deaths, and most of these lives
could be saved through low-cost prevention and treatment
measures, including antibiotics for acute respiratory
infections, oral rehydration for diarrhea, vaccination
against pneumococcal pneumonia and rotavirus, and
nutritional supplements. Proper nutrition is essential to
fight disease effectively because malnutrition weakens the
immune system and reduces resistance to diseases. Iron,
zinc and vitamin A deficiencies have the severest impact on
child morbidity and mortality, and these are also the most
prevalent in developing countries because staple crops such
as rice and white maize are naturally deficient in these
compounds (Freedman et al. 2005).
There has been strong progress towards MDG4 in some
parts of the world, such that the overall infant mortality rate
fell from 12.4 million children per year in 1990 to 8.8
million in 2008, a drop of 28% (UN 2009, 2010a). The
greatest improvements have been seen in North Africa,
Eastern and Western Asia, Latin America and the Carib-
bean, with substantial progress in some of the world’s
poorest countries (Bangladesh, Bolivia, Eritrea, Ethiopia,
Lao People’s Democratic Republic, Malawi, Mongolia,
Mozambique, Nepal and Niger). However, the rest of sub-
Saharan Africa has fallen well behind and now accounts for
50% of all infant deaths. Also, 1 in 14 children still die
before age five in South Asia.
As stated above, neonatal and under-five mortality is
influenced by maternal health, i.e. the health of women
during pregnancy, childbirth and the postpartum period
(especially during breast-feeding). Approximately one in
six women die in pregnancy or childbirth in developing
countries, compared to 1 in 30,000 in Europe (WHO/
UNICEF 2010). Over half of the deaths result from hem-
orrhage and hypertension, 20% involve comorbidity factors
such as malaria and HIV, and 10% result from complica-
tions due to the lack of skilled midwives. MDG4 aims to
reduce maternal deaths by 75% and increase the availability
160
160
100
120
140
20
20
40
60
80
$US per hectare
Bt cotton
Conventional cotton
0
Family male Family femaleHired maleHired femaleAll laborors
Fig. 3 Remuneration (US $/ha) from labor on farms with Bt and
conventional cotton in rural India (Subramanian et al. 2010)
Plant Cell Rep
123

Page 8

of skilled medical personnel attending childbirth. Progress
towards MDG4 has been rapid in some countries (particu-
larly Bolivia, China, Ecuador and Egypt), but progress in
others has been poor, with more than 50% of all maternal
deaths now concentrated in six countries (Afghanistan,
Democratic Republic of Congo, Ethiopia, India, Nigeria
and Pakistan). Global rates are listed in Table 1, with
southern sub-Saharan Africa performing worst: the mater-
nal mortality ratio (the ratio of the number of maternal
deaths per 100,000 live births) in that region increased from
171 in 1990 to 381 in 2008 (UN 2009).
The role of plant biotechnology: improved nutrition
Malnutrition contributes to poor maternal health and (both
directly and indirectly) to poor childhood health. Various
strategies have been proposed to deal with micronutrient
deficiencies including the provision of mineral supple-
ments, the fortification of processed food, the biofortifica-
tion of crop plants at source with mineral-rich fertilizers
and the implementation of breeding programs to generate
mineral-rich varieties of staple crops, and the use of bio-
technology for nutritional improvement (Go ´mez-Galera
et al. 2010). Among these approaches, only conventional
breeding and genetic engineering provide germplasm as a
permanent and sustainable resource, and only genetic
engineering allows the introduction of genes from any
source directly into local varieties.
Perhaps, the best example of genetic engineering for
nutrient enhancement in a developing country context is
‘Golden Rice’, which is enriched for b-carotene (pro-
vitamin A). This compound can be converted into retinal
(the major functional form of vitamin A) by humans and
other herbivorous/omnivorous mammals. Non-engineered
cereal grains including rice and maize are poor sources of
b-carotene, and polished rice grains contain no b-carotene
at all. Vitamin A is required for vision and the correct
functioning of the immune system. Vitamin A deficiency
affects 127 million people in developing countries,
including 25% of pre-school children, causing more than
half a million cases of permanent blindness in children and
2.2 million deaths per year (UNICEF 2006). Therefore,
many researchers have attempted to elevate b-carotene
levels in staple cereals by introducing the corresponding
metabolic pathway. The first significant advance was
‘‘Golden Rice 1’’, where the entire b-carotene biosynthetic
pathway was reconstructed in the endosperm by expressing
daffodil (Narcissus pseudonarcissus) phytoene synthase
and lycopene b-cyclase, and a bacterial (Erwinia uredo-
vora) phytoene desaturase; the resulting grains contained
up to 1.6 lg/g of carotenoids by dry weight (Ye et al.
2000). Later, the daffodil phytoene synthase gene was
substituted with the equivalent gene from maize, resulting
in ‘‘Golden Rice 2’’, in which the total carotenoid content
of the endosperm increased to 37 lg/g dry weight (Paine
et al. 2005). Both Golden Rice lines were donated to the
Oceania
Developing regions
Developed regions
Northern Africa
Transition countries of South-Eastern Europe
CIS Europe
Eastern Asia
Latin America/Caribbean
Western Asia
2008
1990
2015 target
Southern Asia
CIS Asia
South-Eastern Asia
0 20 40 60 80 100120140160180200
Sub-Saharan Africa
Fig. 4 Under-five mortality
rate per 1,000 live births, by
region, 1990 and 2008,
compared to 2015 MDG targets.
Source: UN (2010a)
Plant Cell Rep
123

Page 9

Golden Rice Humanitarian Board, and up to six events of
Golden Rice 2 were developed in the background of the
American Kaybonnet variety, with one event selected for
regulatory approval and commercialization. This line pro-
vides enough b-carotene in a 100-g portion of milled rice to
achieve the recommended daily intake (RDI) of vitamin A
for a child under five (Virk and Barry 2009) and could
therefore prevent vitamin A deficiency (VAD) if consumed
on a regular basis. Local popular rice varieties have been
selected in several countries with widespread VAD (Ban-
gladesh, India, Indonesia, The Philippines and Vietnam),
and it is likely Golden Rice will be commercially available
by 2012 in at least The Philippines and Bangladesh, the
other countries following later (Zeigler 2009). There has
been widespread criticism of the length of time it has taken
to achieve regulatory approval and the barriers that have to
be overcome to achieve adoption, a subject we discuss in
detail below (Potrykus 2010).
Another key nutrient relevant in MDG4 and MDG5 is
folic acid. Deficiency for folic acid in pregnancy leads to
neural tube defects in the fetus and a greater chance of
abortion or complications during delivery. Pregnant
women require at least 600 mg of folate per day, but rice
and maize provide nowhere near adequate amounts.
Whereas processed food is supplemented with folic acid in
the west, developing countries have not implemented sus-
tainable folic acid supplementation programs. Folate syn-
thesis in plants involves two separate pathways (the pterin
and para-aminobenzoate branches) whose products are
eventually conjugated together. Folate biofortification in
rice seeds has been achieved by overexpressing two Ara-
bidopsis thaliana genes, one from each of the pathways,
resulting in a 100-fold enhancement. This means that 100 g
of polished grains contains four times the RDI for folate
(Storozhenko et al. 2007).
Although plants engineered to accumulate single nutri-
ents are beneficial, they address only individual micronu-
trient deficiencies and would ultimately serve to displace
rather than prevent malnutrition. For example, in the
future where individual rice varieties with higher levels of
b-carotene, folate, iron, zinc and other micronutrients are
approved and widely available, people might have to
choose between nutrients because it would be difficult to
eat enough rice to cover all requirements. Two solutions
offer themselves, i.e. the creation of nutritionally improved
varieties that have such high levels of nutrients that only
small portions are required (allowing a mixed meal of
different varieties to satisfy all nutritional requirements) or
the creation of varieties simultaneously enhanced for
multiple nutrients. The latter would be simpler and more
economical although the technical hurdles would be more
difficult to overcome.
In an effort to address this issue, transgenic maize plants
simultaneously enhanced for carotenoids, folate and
ascorbate provide the first example of a nutritionally
enhanced crop targeting three entirely different metabolic
Table 1 Maternal mortality
ratio (uncertainty interval) per
100,000 live births by region
and country (Hogan et al. 2010)
19902000 2008
Asia-Pacific14 (13–15) 10 (9–11)8 (8–9)
Asia, central72 (68–77)60 (56–64) 48 (45–52)
Asia, east 86 (76–98) 55 (48–62)40 (35–46)
Asia, south560 (391–794) 402 (293–555) 323 (232–444)
Asia, southeast248 (187–337) 212 (155–293) 152 (112–212)
Australasia 7 (6–8)6 (5–7) 6 (5–7)
Caribbean 348 (234–518) 323 (218–483) 254 (168–372)
Europe, central 34 (31–37)18 (17–20) 13 (12–14)
Europe, eastern43 (39–48) 41 (37–45)32 (29–35)
Europe, western 10 (10–11)8 (8–9)7 (7–8)
Latin America, Andean229 (176–295)156 (116–205)103 (77–134)
Latin America, central85 (77–94)70 (64–78)57 (51–63)
Latin America, southern54 (49–60) 44 (39–49) 41 (36–45)
Latin America, tropical113 (66–184) 71 (47–107) 57 (37–87)
North Africa/Middle East 183 (154–218)111 (92–135)76 (61–94)
North America, high income11 (10–12)13 (11–15)16 (14–18)
Oceania416 (252–649)329 (202–518)279 (174–434)
Sub-Saharan Africa, central732 (488–1,101)770 (535–1,108)586 (392–839)
Sub-Saharan Africa, east690 (574–842)776 (639–948)508 (430–610)
Sub-Saharan Africa, southern171 (132–222)373 (280–499)381 (288–496)
Sub-Saharan Africa, west582 (485–709)742 (608–915)629 (508–787)
Plant Cell Rep
123

Page 10

pathways (Naqvi et al. 2009). This was achieved by trans-
ferring four genes into a white maize variety resulting
in a 407-fold elevation of b-carotene levels (57 lg/g
dry weight), 6.1-fold increase in ascorbate (106.94 lg/g dry
weight) and a 2-fold increase in folate (200 lg/g dry
weight). The decision to engineer three pathways at the
same time rather than crossing lines individually engineered
to increase the level of single nutrients was taken because
the crossing strategy is slow and inefficient (Zhu et al.
2008). The simultaneous transformation strategy results in
all the transgenes integrating at a single locus, which
therefore remains stable through subsequent generations.
Pregnant women and infants also tend to have higher
mineral requirements and particularly fall victim to defi-
ciencies in iron (recommended daily allowance/adequate
intake = 8 mg/day for males but 18 mg/day for women
of reproductive age and 27 mg/day in pregnancy), zinc
(RDA/AI = 8–13 mg/day for all) and calcium (RDA/
AI = 1,000–1,300 mg/day for all). Calcium is essential for
bone development, iron is needed for the synthesis of
hemoglobin and various enzymes, and zinc is a cofactor for
numerous enzymes and transcription factors. Mineral bio-
fortification requires different strategies to vitamin biofor-
tification because minerals are not synthesized de novo like
organic compounds and must be sequestered from the
environment (Go ´mez-Galera et al. 2010). One notable
recent report describes the hyperaccumulation of iron in
rice plants transformed with two genes, one encoding
nicotianamine synthase (which is required for iron trans-
port through the vascular system) and the other ferritin
(which increases the capacity for iron storage) (Wirth et al.
2009). Many, although not all, of the channels and trans-
porters that increase iron uptake also work with zinc often
resulting in co-accumulation. Calcium levels in carrot roots
and lettuce leaves were increased by 30–100% by over-
expressing the H?/Ca2?transporter sCAX1, and this is
another strategy that could be transferred to cereal crops
(Morris et al. 2008; Park et al. 2009).
The role of plant biotechnology: using plants to produce
inexpensive (oral) vaccines
Plants have been used for medicinal purposes for hundreds
of years, but it is only recently that they have been delib-
erately engineered to produce specific pharmaceutical
products (Twyman et al. 2005). Two broad strategies are
envisaged. In the first, plants are simply an expression
platform like any other (e.g. bacteria, yeast or mammalian
cells), and the product is purified and formulated in the
standard manner. In the second, plants are used as both the
expression platform and the delivery vehicle, and this
category includes the use of plants to produce oral vac-
cines. The principle is that a recombinant subunit vaccine
is expressed in an edible plant organ such as potato tubers
or cereal seeds and then administered as part processed
food (e.g. puree or juice) which would be suitable for the
large-scale immunization of adults and children in devel-
oping country settings (Yusibov and Rabindran 2008).
Plants have been used to produce many different vaccine
candidates, including oral vaccines to prevent hepatitis B,
cholera, rabies and diarrheal diseases in humans that have
been successful in phase I clinical trials (Tiwari et al.
2009). The main technical challenge with oral vaccines is
to induce a sufficient immunological response through
mucosal immunity, which can be achieved by linking the
antigen to a mucosal adjuvant such as the labile enterotoxin
B subunit (LTB). The LTB protein was the first plant-
derived recombinant oral antigen to be tested in phase I
trials (Tacket et al. 1998).
Since diarrheal diseases account for a large proportion
of under-five deaths in developing countries, the use of
plant-derived oral vaccines to prevent sickness and diar-
rhea is the most relevant application of the technology in
the context of MDG4. As proof of this concept, Tacket
et al. (2000) developed an oral vaccine against Norwalk
virus (which causes travelers’ sickness), and the results of
the phase I trials were similar to those with LTB, with
nearly all of the volunteers who participated in the trial
showing significant increases in the numbers of IgA-anti-
body forming cells (AFCs) and six also showing increases
in IgG AFCs. There were also noticeable increases in
serum IgG and stool IgA against the virus.
The provision of edible vaccines against common dis-
eases in school children in developing countries could give
parents additional encouragement to bring their children to
school. For example, an oral vaccine comprising the
cholera toxin subunit (CTB) expressed in rice under the
control of an endosperm-specific promoter, induced anti-
gen-specific mucosal and systemic immune responses in
mice, and would be an excellent candidate to develop for
human use in the developing world (Nochi et al. 2007).
Advantages of vaccines delivered in cereal grains include
the increased stability in storage and after administration,
addressing distribution problems and the lack of a cold
chain, and also prolonging the window of opportunity to
induce an effective immune response after administration.
The rice/CTB vaccine could be stored at room temperature
for more than 18 months without degradation, and once
administered it resisted the harsh environment in the
stomach because it accumulated in endosperm storage
organelles known as protein bodies which provided
shielding (bioencapsulation). Oral immunization induced
CTB-specific serum IgG and mucosal IgA, and conferred
protection because serum from immunized mice prevented
cholera toxin binding to GM1-ganglioside, which causes
severe diarrhea.
Plant Cell Rep
123

Page 11

As well as their use in humans, oral vaccines produced
in plants also provide an inexpensive and convenient way
to prevent disease in domestic animals, which would also
help to increase the productivity and economic prosperity
of farmers. Hundreds of vaccines for animal diseases have
been expressed in plants, many proving efficacious in
challenge studies. One worth particular mention is the
recently developed vaccine against Newcastle disease in
poultry, which was developed by Dow AgroSciences and
became the first plant-derived vaccine to receive USDA
approval. This product was developed to test the regulatory
pathway and has not yet been marketed, but it has cleared
the way for other vaccines produced using the same plat-
form technology.
Despite the demonstrated efficacy of plant-derived
vaccines, deployment for human populations seems unli-
kely at present. The approval process for Golden Rice
indicates that there is an unwritten tiered approach to
acceptability, with crops engineered to prevent pests and
diseases now widely accepted, those with improved nutri-
tional traits receiving guarded approval but still distrust of
those with value-added products such as pharmaceuticals
in an uncertain regulatory environment (Spok et al. 2008).
There is a general regulatory consensus that crops pro-
ducing pharmaceutical products would need to be segre-
gated from food crops to prevent adventitious exposure to
the bioactive substance and reduce the likelihood of out-
crossing (Spok et al. 2008). An additional challenge spe-
cific to oral vaccines is achieving consistent doses of the
antigen when delivering as part-processed food or feed/
fodder. Paul and Ma (2010) present a critical review of
plant-derived oral vaccines and the challenge of developing
effective delivery strategies.
MDG 6: Combat HIV/AIDS, malaria and other diseases
Overview
HIV/AIDS, malaria and tuberculosis represent the major
public health challenges in the world’s poorest countries
(Fig. 5). HIV is a virus often transmitted not only through
sexual contact but also by intravenous drug use and from
mothertochild.Thediseasehascausedmorethan25million
deaths since it was first recognized in 1981, and 33.4 million
people are currently thought to be HIV positive, 95% of
whom live in developing countries (UNAIDS/WHO 2009).
AIDS remains the leading cause of adult mortality in Africa
today, and the sixth leading cause of death in the world.
MDG6 aims to halt and reverse the spread of HIV/AIDS by
2015 and provide wider access to HIV drugs. Malaria is
causedbyparasitesofthegenusPlasmodium,transmittedby
mosquitoes.Itaffects350–500millionpeopleeachyear,and
one million die from the disease, particularly children under
five and pregnant women, who are particularly vulnerable.
As for HIV/AIDS, the poor are disproportionately affected
and make up the vast majority of the 40% of the world’s
population living in high-risk areas. MDG6 aims to reduce
theincidenceofmalariagloballyandprovideaccesstodrugs
and mosquito nets. Tuberculosis is a respiratory disease
transmitted by aerosol, caused by the bacterium Mycobac-
terium tuberculosis. More than one-third of the world’s
population is thought to be infected, and the disease kills 1.7
million people each year, predominantly in developing
countries (Elı ´as-Lo ´pez et al. 2008). An approved tubercu-
losis vaccine, BCG (Bacille Calmette Gue ´rin), is used
worldwideandisadministeredtoapproximately100million
infants per year providing good protection against the most
severe childhood forms of the disease, and antibiotics can
alsobeusedtotreatinfections.However,theseresourcesare
not easily accessible in developing countries, hence the
prevalence of the disease. HIV activates dormant tubercu-
losis, and more than 10 million people worldwide are
infected with both HIV and tuberculosis.
The role of plant biotechnology (HIV)
Barrier methods help to prevent new HIV infections as well
as protecting against other diseases and unplanned preg-
nancies, and one of the objectives under the HIV compo-
nent of MDG6 is to increase education about the disease
and the availability of condoms and other barrier devices.
However, gender inequality and cultural preferences (see
MDG3) place many women in the position of being unable
to negotiate condom use without male cooperation, even if
the male is known to be HIV positive (Population Council
2000; Padian et al. 1998).
Millions of deaths per year
23014567
Lower respiratory infections
HIV/AIDS
Malaria
Diarrhea
Tuberculosis
Measles
Whooping cough
Tetanus
Meningitis
Syphilis
Fig. 5 Ranking of fatal diseases in the developing world (millions of
deaths per year). Where accurate figures are not known, the two bars
represent minimum and maximum estimates. Source: World Health
Organization
Plant Cell Rep
123

Page 12

Microbicides that are applied well in advance of sexual
intercourse would place the means to control HIV infection
in the hands of monogamous women. Several candidate
products have been developed based on surfactants, HIV-
neutralizing antibodies and lectins, alone or in combination
with anti-retroviral drugs (Ramessar et al. 2010). One
drawback of this approach is that antibodies must be used
in very high doses (up to 1 g per application) because of
their stoichiometric mechanism of action and to ensure
enough of the active ingredient survives the harsh mucosal
environment. The microbicide would have to be applied
daily, perhaps several times a day, and with the anticipated
demand this would require the relevant antibodies to be
produced on a multi-ton scale which is several orders of
magnitude above current production capacities. Moreover,
antibodies are generally produced by fermentation in
mammalian cells and are therefore among the most
expensive biopharmaceuticals on the market. In order to
supply microbicides to impoverished women in the rural
communities of sub-Saharan Africa and South Asia, a
revolutionary change in production technology would be
necessary.
Plant biotechnology has a role to play in this scenario
because plants provide a key advantage over animal cells
for the production of biopharmaceuticals—the economy of
scale. Increasing the scale of production in animal cells
requires larger fermenters and facilities, whereas plants can
be scaled up much more readily through additional land or
greenhouse space (Ma et al. 2003; Twyman et al. 2005;
Ramessar et al. 2008a, c). Many promising microbicide
compounds have been successfully expressed in transgenic
plants, including the antiviral lectins griffithsin (O’Keefe
et al. 2009) and cyanovirin-N (Sexton et al. 2006). Plant-
derived griffithsin showed broad spectrum activity against
HIV at picomolar concentrations, was directly virucidal by
binding to HIV envelope glycoproteins, and was capable of
blocking cell-to-cell HIV transmission. It was also nonir-
ritating and non-inflammatory in human cervical explants
and in vivo in the rabbit vaginal irritation model. Cyano-
virin-N was produced using hydroponic cultures and was
shown to bind HIV gp120 and protect T cells from HIV
infection in vitro.
HIV-neutralizing antibodies have also been produced in
plants, including 2G12 (produced in tobacco and maize)
(Ramessar et al. 2008b; Rademacher et al. 2008; Strasser
et al. 2009), 2F5 (produced in tobacco) (Floss et al. 2009)
and 4E10 (produced in tobacco). The HIV-neutralizing
activity of tobacco and maize 2G12 was equal to or
superior to that of the same antibody produced in CHO
cells, and 2G12 has now been produced under GMP con-
ditions in preparation for phase I clinical trials (the first
plant-derived antibody to reach clinical development,
through a publicly funded initiative). Another interesting
example is the production of a combined microbicide
candidate to minimize the risk of viral adaptation and the
appearance of resistant strains and to provide sufficient
cross-clade protection (Ramessar et al. 2010). Sexton et al.
(2009) combined the HIV-neutralizing antibody b12 with
cyanovirin-N and produced the fusion protein in transgenic
tobacco. The fusion protein was more potent against HIV
than either individual component.
The role of plant biotechnology (malaria)
Plants have also been used to express malarial antigens in
an attempt to develop an inexpensive vaccine candidate,
but such products are at a very early stage in development
and would not be expected in the clinic for at least 5 years.
However, plants are not solely used for the production of
recombinant proteins—they are also valuable sources of
antimalarial drugs, such as artemisinin. The cost of
extracting artemisinin from its source means the drug is too
expensive for the poorest people in developing countries,
those most in need of it. The cost could be reduced by
recreating the metabolic pathway leading to artemisinin in
a plant species that is more accessible or easy to culture
although there is currently insufficient knowledge of the
enzymatic steps in the pathway (Ma et al. 2009).
The role of plant biotechnology (tuberculosis)
Plant-derived vaccine candidates against tuberculosis have
been produced in tobacco and Arabidopsis, with some evi-
dencethattheygenerateimmunecorrelatesofprotection.For
example, Rigano et al. (2004) produced transgenic Arabid-
opsis plants expressing the immuno-dominant tuberculo-
sis antigen ESAT-6 fused to a mucosal adjuvant and fed the
oral vaccine to mice. They found that the fusion protein
inducedanimmuneresponsebutunfortunatelynotenoughto
reduce the bacterial load and to protect mice against disease
challenge. More recently, ESAT-6 and Ag85B were expres-
sed in tobacco as fusions with an elastin-like peptide to
increase their accumulation (Floss et al. 2010). Purified
TBAg-ELP was obtained by inverse transition cycling and
tested in mice and piglets for safety and efficacy. Antibodies
recognizing mycobacterial antigens were produced in both
species. A T-cell immune response recognizing the native
mycobacterial antigens was detected in mice.
In a related approach, Elı ´as-Lo ´pez et al. (2008) pro-
duced transgenic tomato plants expressing interleukin-12, a
key cytokine. Oral delivery studies in which crude fruit
extracts (lyophilized preparations) were fed to mice
infected with various strains of the tuberculosis agent
showed that the animals were more resistant to the disease
and suffered less lung tissue damage having ingested the
tomato extracts.
Plant Cell Rep
123

Page 13

MDG 7: Ensure environmental sustainability
Overview
The objectives under MDG7 are to integrate the princi-
ples of sustainable development into country policies and
programs and reverse the loss of environmental resour-
ces, reduce biodiversity loss significantly by 2010, reduce
the proportion of the population without sustainable
access to safe drinking water and basic sanitation to 50%
of initial levels by 2015, and achieve a significant
improvement in the lives of at least 100 million slum
dwellers by 2020.
Sustainable development requires that natural resources
are conserved, and while progress is being made in all
areas, the rate of environmental destruction is still alarm-
ingly high. Although urbanization and industrialization
play an important role in this process, agriculture also has a
major impact. As discussed above, access to safe water is
limited in many countries because of pollution with both
pathogens and chemical residues, particularly the run-off of
agrochemicals. The 2010 target for biodiversity conserva-
tion has been missed, and key habitats for threatened
species are not being adequately protected (UN 2010a).
The rate of deforestation is slowing but even so averaged
5.2 million hectares per year over the last decade. More
carbon dioxide is being released into the atmosphere than
ever before, 35% more than 10 years ago. This trend needs
to be stabilized and reversed if MDG7 is to be achieved.
The role of plant biotechnology
Plant biotechnology has a critical role to play in the
improvement of environmental sustainability. Some of the
major impacts have already been discussed in the context
of other MDGs and will only be summarized here. These
are: (1) the development of crops that require less water
(drought-tolerant crops), thereby releasing more freshwater
resources for drinking and for infrastructure development;
(2) the development of high-yielding crops that produce
adequate yields on smaller plots, thereby reducing the need
for forests to be cut down to provide agricultural land; (3)
the development of crops that are resistant to weeds, insect
pests and pathogens to reduce chemical use and fuel con-
sumption. The deployment of Bt crops has reduced the use
of pesticides, also saving on fossil fuels required for
spraying. The deployment of herbicide-tolerant crops has
reduced fuel use and CO2emissions by limiting the need
for plowing, and conserving soil and moisture by encour-
aging no-tilling agriculture. The cumulative reduction in
pesticide use for the period 1996–2008 was approximately
356,000 tons (8.4%), which is equivalent to a 16.1%
reduction in the associated net environmental impact as
measured by the environmental impact quotient (EIQ). The
corresponding data for 2008 alone revealed a reduction of
34,600 tons of pesticides (9.6%) and a reduction of 18.2%
in EIQ (Brookes and Barfoot 2010). In countries such as
India, China, Argentina and Brazil, which are the most
enthusiastic adopters of Bt agriculture after the US and
Canada, the greatest impact of Bt has been the reduction in
the number of pesticide sprays (Naranjo 2009). In India, for
example, the reduction is from 16 down to 2–3 sprays per
growing season (Qaim et al. 2006; Karihaloo and Kumar
2009).
MDG8: Develop a global partnership for development
The MDGs represent a global partnership for development,
and developing countries must take on the primary
responsibility to work towards achieving the first seven
MDGs. They must do their part to ensure greater
accountability and efficient use of resources. But for
developing countries to achieve this, it is absolutely critical
that developed countries deliver on their end of the bargain
with more effective aid, more sustainable debt relief and
fairer trade rules, well in advance of 2015.
The objectives in MDG8 are to (a) address the special
needs of least developed countries, landlocked countries
and small island developing states; (b) develop an open,
predictable, nondiscriminatory trading and financial sys-
tem; (c) deal comprehensively with developing countries’
debt; (d) make available the benefits of new technologies in
cooperation with the private sector, especially information
and communications. In terms of plant biotechnology, the
fourth objective is the most relevant, and we already have
several examples of how this has been put into practice
with the Golden Rice Humanitarian Board and WEMA
(see above). These programs form the basis for technology
donation for humanitarian purposes, where technology can
be used royalty-free for subsistence agriculture or to alle-
viate poverty, hunger, malnutrition and disease. The two
examples cited above focus in one case on nutritional
improvement and in the other on the avoidance of starva-
tion during drought, but the same principles apply to
pharmaceutical plants. For example, all the partners in the
Pharma-Planta consortium (http://www.pharma-planta.org
), which has established the regulatory pathway necessary
to produce HIV-neutralizing antibodies in plants (Spok
et al. 2008), have signed up to a humanitarian use clause
which allows all the technology developed in the project
(as well as any necessary background IP) to be used roy-
alty-free for humanitarian purposes. The HarvestPlus
Challenge Program is a similar concept although focusing
on conventional biofortification strategies and mostly
eschewing genetic engineering.
Plant Cell Rep
123

Page 14

Because MDG8 will depend on political cooperation
between developed and developing countries, this is the
appropriate juncture to discuss the role of politics in plant
biotechnology and the barriers to adoption that have been
erected (Farre et al. 2009). Plant biotechnology is one of a
raft of strategies that can be combined to make progress
towards the MDGs, and many of the technological barriers
have been overcome. However, the impact of this scientific
progress is being neutralized by the unwillingness of pol-
iticians to see beyond immediate popular support and to
take politically controversial decisions that would in the
short to medium term save millions of lives and in the long
term would make a significant impact on the health, well-
being and economic prosperity of the world’s poorest
people. The problem is essentially that whereas political
decision-making should be based on rational scientific
evidence, it is more often dictated by certain NGOs with
dubious agendas and the media, which thrives on sensa-
tionalism (Farre et al. 2010). Unfortunately, this feeds back
in such a way that those charged with regulating biotech-
nology are pressured into implementing excessive regula-
tion, which extends development times unnecessarily and
results in many more lives being put at risk (Farre et al.
2010).
Conclusions and outlook
Each of the MDGs reflects one or more fundamental
aspects of socioeconomic development in countries that
depend predominantly on subsistence agriculture to feed
their populations. Therefore, it seems natural that the
improvement of agricultural productivity should form the
keystone upon which the framework of progress can be
built. In this context, technological solutions to improve
agricultural productivity and sustainability can be regarded
as a valuable approach to ensure rapid progress towards the
MDGs, particularly technologies that improve yield, vigor
and nutritional value in staple crops and allow the pro-
duction of added-value products such as pharmaceuticals.
The prospects of implementation vary considerably,
with some products already deployed and having a strong
impact, others on the verge of approval, and others unlikely
to see large-scale deployment by 2015 if at all. The success
of Bt crops in India and China is likely to be repeated in
Africa and South Asia as these have reduced hunger and
led to economic prosperity within a remarkably short time.
Many additional Bt varieties are waiting in the wings, and
perhaps, even more exciting is the prospect of multi-trait
crops simultaneously protected against a range of pests and
viral and microbial diseases, as well as drought and other
environmental factors. Within the next 2 years, we should
also see the first commercial release of Golden Rice, and
this will hopefully open the door for a range of additional
nutritionally enhanced crops that will address food inse-
curity in a sustainable manner.
The prospect of more ambitious technologies such as the
use of plants to produce vaccines and drugs is unlikely to
have an immediate impact in the developing world because
the regulatory burden would be high and the construction
of contained facilities would provide no further advantage
compared to production in the west. In the short term, it is
more likely that plant-derived pharmaceuticals will fill
niche markets in the west and then spread to high-volume,
low-margin products as yields improve, but the royalty-free
donation of technologies and products may lower the cost
of goods to the extent required to meet the demands of
local health authorities in developing countries.
Most importantly, it is clear that the irrational political
handling of plant biotechnology must be resolved so that
developing countries are not put in the position of choosing
between principles and lives. National and International
funding agencies and charitable organizations should
encourage collaborative projects with universities and
other research organizations in target countries so that
capacity-building programs can prepare a generation of
local experts to establish their own research facilities,
enabling them to operate independently, without political
pressure, to develop sustainable solutions for their own
populations. Most importantly, there must be leadership
from the top—the EU needs to stop pandering to activists
and the media, and should take decisions based on rational
scientific evidence in order to help the world’s most vul-
nerable people. Only when bold decisions are made in
Europe and elsewhere in the industrialized world, can the
fruits of our scientific endeavor be used to accelerate pro-
gress towards the MDGs.
Acknowledgments
Ministry
BFU2007-61413); European Research Council Advanced Grant
BIOFORCE; Center Consolider, MICINN, Spain; COST Action
FA0804, Associated Unit CAVA and SmartCell, FP7 Integrated
project.
Research in our laboratory is supported by
Science and Innovation-MICINN,of Spain(Grant
Appendix 1: The Millennium Development Goals in full
(UN 2010a)
Goal 1: Eradicate extreme poverty and hunger
Target 1A: Halve the proportion of people living on
less than $1 a day
Target 1B: Achieve decent employment for women,
men, and young people
Target 1C: Halve the proportion of people who suffer
from hunger
Plant Cell Rep
123

Page 15

Goal 2: Achieve universal primary education
Target 2A: By 2015, all children can complete a full
course of primary schooling, girls and boys
Goal 3: Promote gender equality and empower women
Target 3A: Eliminate gender disparity in primary and
secondary education preferably by 2005 and at all
levels by 2015
Goal 4: Reduce child mortality rate
Target 4A: Reduce by two-thirds, between 1990 and
2015, the under-five mortality rate
Goal 5: Improve maternal health
Target 5A: Reduce by three quarters, between 1990
and 2015, the maternal mortality ratio
Target 5B: Achieve, by 2015, universal access to
reproductive health
Goal 6: Combat HIV/AIDS, malaria, and other diseases
Target 6A: Have halted by 2015 and begun to reverse
the spread of HIV/AIDS
Target 6B: Achieve, by 2010, universal access to
treatment for HIV/AIDS for all those who need it
Target 6C: Have halted by 2015 and begun to reverse
the incidence of malaria and other major diseases
Goal 7: Ensure environmental sustainability
Target 7A: Integrate the principles of sustainable
development into country policies and programs, and
reverse loss of environmental resources
Target 7B: Reduce biodiversity loss, achieving, by
2010, a significant reduction in the rate of loss
Target 7C: Halve, by 2015, the proportion of people
without sustainable access to safe drinking water and
basic sanitation
Target 7D: By 2020, to have achieved a significant
improvement in the lives of at least 100 million slum-
dwellers
Goal 8: Develop a global partnership for development
Target 8A: Develop further an open, rule-based,
predictable, non-discriminatory trading and financial
system
Target 8B: Address the special needs of the least
developed countries (LDC)
Target 8C: Address the special needs of landlocked
developing countries and small island developing
states
Target 8D: Deal comprehensively with the debt
problems of developing countries through national
and international measures in order to make debt
sustainable in the long term
Target 8E: In co-operation with pharmaceutical com-
panies, provide access to affordable, essential drugs in
developing countries
Target 8F: In co-operation with the private sector,
make available the benefits of new technologies,
especially information and communications
References
Akobundu IO (1991) Weeds in human affairs is sub-Saharan Africa.
Weed Tech 5:680–690
APCoAB (Asia-Pacific Consortium on Agricultural Biotechnology)
(2006) Bt cotton in India: a status report. ICRASTAT, New
Delhi
Balga P (2010) After acrimonious debate, India rejects GM eggplant.
Science 327:767
Bhatnagar-Mathur P, Vadez V, Sharma KK (2008) Transgenic
approaches for abiotic stress tolerance in plants: retrospect and
prospects. Plant Cell Rep 27:411–424
Bourguet D (2004) Resistance to Bacillus thuringiensis toxins in the
European corn borer: what chance for Bt maize? Physiol
Entomol 29:251–256
Brookes G (2008) The benefits of adopting GM insect resistant (Bt)
maize in the EU: first results from 1998–2006. Int J Biotechnol
10:148–166
Brookes G, Barfoot P (2010) GM crops: global socio-economic and
environmentalimpacts1996–2008.
Dorchester
Castiglioni P, Warner D, Bensen RJ, Anstrom DC, Harrison J,
Stoecker M, Abad M, Kumar G, Salvador S, D’Ordine R,
Navarro S, Back S, Fernandes M, Targolli J, Dasgupta S, Bonin
C, Luethy MH, Heard JE (2008) Bacterial RNA chaperones
confer abiotic stress tolerance in plants and improved grain yield
in maizeunderwater-limited
147:446–455
Christou P, Twyman RM (2004) Potential of genetically engineered
crops to address food insecurity. Nutr Res Rev 17:23–42
Christou P, Capell T, Kohli A, Gatehouse JA, Gatehouse AM (2006)
Recent developments and future prospects in insect pest control
in transgenic crops. Trends Plant Sci 11:302–308
DFID (2010) The politics of poverty: elites, citizens and states.
Findings from ten years of DFID-funded research on governance
and fragile states 2001–2010. DFID, London, UK
Ejeta G, Rich PJ, Mohamed A (2007) Dissecting a complex trait to
simpler components for effective breeding of sorghum with a
high level of Striga resistance. In: Ejeta G, Gressel J (eds)
Integrating new technologies for Striga control—towards ending
the witch hunt. World Scientific, Singapore, pp 87–98
Elı ´as-Lo ´pez AL, Marquina B, Gutie ´rrez-Ortega A, Aguilar D,
Gomez-Lim M, Herna ´ndez-Pando R (2008) Transgenic tomato
expressing interleukin-12 has a therapeutic effect in a murine
model of progressive pulmonary tuberculosis. Clin Exp Immunol
154:123–133
Fan S, Chan-Kang C, Mukherjee A (2005) Rural and urban dynamics
and poverty: evidence from China and India. International Food
Policy Research Institute, Washington, DC
FAO (2009a) Maize, rice and wheat: area harvested production
quantity yield. FAO, Rome
PG EconomicsLtd,
conditions.PlantPhysiol
Plant Cell Rep
123