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Date:

July 12, 2002

Subject:

Formidable Revolution; 21st Century Sanke Oil; Labeling Confusion

 

Today in AgBioView - July 13, 2002

* The Brothers From Another Planet
* Organic, Conventional and Genetically Engineered Foods
* Re: Agribiotech and big business
* Biotech and Farmers' Rights Sustainable Agr Development Perspective
* Pew Webcast - Labeling GM Foods: Communicating or Creating Confusion?
* IPR Is Not A Constraint To Science
* 'Extremely Low' Risk of GM Transfer
* Genetic Improvement: A Review
* Pharm Farming , It's Not Your Father's Agriculture

The Brothers From Another Planet

- A A Gill, Sunday Times, July 7, 2002

Bitter Harvest (Sunday, BBC2), the excellent series on genetic
engineering, contained one of the most extraordinary images of the week:
Amish farmers harvesting genetically modified, nicotine-free tobacco
plants. These are people who won't use zips because they're a modern
aberration. It was impressive, if spiritually confused. The tobacco itself
might one day contain a cure for cancer, which is also confusing. In fact,
cancer drugs could be grown bespoke, your specific medication planted from
seed. Even if just 5% of the promises of genetic research turn out to be
10% true, then medicine and food are going to see a formidable revolution
in the next 50 years.

If the 19th century was all about engineering and physics, and the 20th
about electronics and computing, then the 21st looks set to be the century
of biology. This understated and even-tempered trio of programmes tried to
maintain some semblance of balance in its reporting, but it is really
terribly difficult.

The green lobby may shout loudest, but when, on the one hand, you have a
quiet, rational biologist talking about cures for Third World diseases and
feeding the hungry, and, on the other, you have a man dressed as a chicken
who shouts that it's not right because Mother Nature told him, well, it's
difficult to maintain a straight face. It used to be that the very
efficient ecolobby had all the romantic and emotional arguments, but with
this, the vision and the lump in the throat belonged to the men in white
coats. The guys with carnival hats looked like fundamentalist Luddites and
Tolkienesque fantasists.

The argument against GM research boils down to: "We've never done this
before, so let's not risk it; and if it does work, a lot of people we
don't like are going to make money out of it." That's not a particularly
enlightened or winning argument. Literally and metaphorically, it's
fruitless. You can't stop people discovering things, and you can't stop
humans being inquisitive. It's part of our natural and modified genetic
code. I can't wait to discover what becomes of the goats whose udders have
been crossed with spiders so they lactate the strongest rope in the world.

**********************************************

Organic, Conventional and Genetically Engineered Foods

- Douglas Powell July 10, 2002, www.foodsafetynetwork.ca

Why did the Toronto opening of Whole Foods Markets -- a grocery store few
mortals can afford to shop at ñ create an orgy of hype and hucksterism,
largely for its selection of so-called organic and natural foods? Why does
Prince Charles continue to praise the so-called virtues of organic
farming?

Why do people buy organic foods? Consumers often cite "tastier", "safer",
and "healthier" as reasons for paying the premium for organic products.
However claims of safer and more nutritious have never been substantiated.
A small, unscientific sample commissioned by the Globe and Mail and CTV
comparing the nutritional attributes of organic and conventional foods
concluded exactly what numerous, large, scientifically valid studies have
found ñ organic foods have essentially the same nutritional content and
conventional produce.

A comprehensive report published earlier this year in the the journal,
Critical Reviews in Food Science and Nutrition by researchers at Otago
University in New Zealand concluded there is no convincing evidence to
back claims that organically grown foods were healthier or tastier than
those grown using chemicals. The nutritional value of food was influenced
by the time of harvest, freshness, storage, and weather, but many studies
claiming organic food had more vitamins and minerals did not take proper
account of these factors.

One year ago, the U.K. Advertising Standards Authority (ASA) upheld four
complaints against claims in a Soil Association leaflet entitled, Five
Reasons To Eat Organic, similar to the 10 Reasons to Eat Organic being
flogged by Whole Foods. The ASA ruled there was no evidence, contrary to
the assertions of the Soil Association, that consumers could taste the
difference, organic was healthy, it was better for the environment, and
organic meant healthy, happy animals. On one claim, the Soil Association
responded that 53 per cent of people buying organic produce did so because
they thought it was healthy. The ASA rightly ruled this did not constitute
any sort of clinical or scientific evidence.

The New Zealand reviewers and others have concluded there were
environmental benefits from growing organically and that organic products
had lower residues of synthetic pesticides. And many consumers believe
that organic is a more sustainable way of farming. Yet contrary to public
opinion, organic produce does contain natural pesticides; in fact, there
is a whole list of naturally-occurring chemicals that are regularly used
in organic production. Further, organic often has lower yields, which
means that more land is required to provide the same amount of food.

Dr. Norman Borlaug, 1970 Nobel Peace Prize laureate, was recently quoted
as saying, "Growing more crops and tree per acre leaves more land for
Nature. Without higher yields, peasant farmers will destroy the wildlands
and species to keep their children from starving. Sustainably higher
yields of crops and trees are the only visible way to save both. Right
now, too many environmental groups are pushing low-yielding, low-input
systems -- such as organic farming -- in the belief that environmental
purity is the primary goal. But what good is pure farming if it takes over
all of the planet's land area? We need a balance of responsible,
high-yielding technologies on our farms so we can produce the food we need
and leave more of the natural landscape for wildlife."

One of those technologies is genetic engineering. A new study from the
Washington-based National Center for Food and Agricultural documented a 46
million pound reduction in pesticide use in the U.S. in 2001 because of
genetically engineered crops such as cotton, canola, soy and field corn.
In crops like sweet corn and potatoes, genetic engineering can
substantially reduce pesticide use. But that is anathema to organic
growers, who insist, for philosophical ñ and marketing -- reasons, on
excluding a technology which, on some crops, is entirely consistent with
the goal of reduced pesticide use and more sustainable farming. In fact,
one of the ways that organic foods are marketed ñ and something some
consumers apparently look for -- is by declaring a zero-tolerance for
genetically modified organisms (without distinguishing between genetic
engineering and other methods to modify genes). Should a gene from the
increasingly popular genetically engineered crops used by North American
farmers appear in organic product, the result is deemed contaminated and
ineligible for organic status.

But how realistic is this apparent zero tolerance? Or is it nothing more
than marketing bumpf? Australian researchers recently reported in the
journal Science that based on an examination of 48 million seeds from 63
fields across southern Australia, canola pollen was indeed carried to
other fields, but in amounts well below internationally recognized levels
for unwanted genetic transfer, and that the amounts were so small that it
would be almost impossible to detect the gene flow using current DNA
assessment methods. Genes move around; they always have. Biology is messy.
And that is why accepted levels or tolerances have always been in place
for seed purity, pesticide drift and other factors.

So even if a particular food is promoted as absolutely free of genetic
modification, it probably isnít. Just like if food is promoted as
nutritionally superior or healthier, it probably isnít. But food, organic
or otherwise, is 21st century snake oil. Farmers, though, may heed the
advice of InterNutrition, the Swiss Association for Research and
Nutrition, which published a comparative review concerning the biological,
conventional and genetic engineering methods used in agriculture and
nutrition in 2000 and concluded that the "scientific literature published
so far shows that all the methods currently available have the right to
exist. The specific combination of all useful approaches offers the
greatest potential for sustainable agriculture and healthy foods."

**********************************************

Re: Agribiotech and big business
From: Ray Shillito Ý

Re: Subject: Agribiotech and big business. from: "Amit Basole"

At the moment it is true that much of the work is being done by what you
call "big business". I am employed in such a business, and it would be
wonderful if I or others with industry experience could get significant
funding to work "on the outside". There are limited funds, and these are
being very well and efficiently used by those who are in Academia and
Institutes. If you want to change the status quo, then work to get
governments to move some of the incredible amounts of money spent on
medical research into research on crops for development. As was clearly
stated a week or two ago at the IAPTC/SIVB congress - a small percentage
of those funds would make a major difference in application of this
technology to the "third world". Unfortunately FAO, WHO etc., ignore the
positive effects of agriculture on sparking development.

Yours sincerely, Ray Shillito, Bayer CropScience

**********************************************

Biotechnology and Farmers' Rights Sustainable Agricultural Development
Perspective

- Gopal Naik, Business Line (The Hindu; India) July 12, 2002

As agriculture provides livelihood for the majority of the Indian
population, achieving a high growth rate and substantial reduction in
poverty depends on the farm sector. While a significant growth rate was
achieved in the 1970s and the 1980s, the 1990s showed signs of a slowdown,
especially in foodgrain production. The demand for food has been
increasing at about 2.75 per cent due to increase in population and
income. In addition, many new problems related to chemical technologies,
irrigation practices and management have also cropped up, raising barriers
to agricultural production.

Some current agricultural technologies have problems of sustainability and
caused more difficulties. Indiscriminate use of chemicals, especially
pesticides, has led to widespread resistance of pests, soil and water
pollution, affected soil fertility, and resulted in higher pesticide
residue levels in foods. Nearly 42 per cent of the crop productivity is
lost due to weeds, pests and diseases and an additional 10-30 per cent due
to post harvest losses. Many importing countries are using this as a
non-price barrier to restrict imports from India. While integrated pest
management and integrated nutrient management practices should have helped
alleviate these problems, the knowledge-intensive nature of these
practices and illiteracy among farmers have prevented their faster
adoption. However, biotechnology seems to offer solutions to these
problems.

Indian agriculture in the new trade regime
The new trade regime initiated in the Uruguay Round of GATT 1994 (WTO)
requires India to shift its agricultural policy focus from that of
self-sufficiency to developing competitiveness. Technological solutions
are becoming more important as some deficiencies in the institutional set
up can be overcome through appropriate technology. Biotechnology is
considered important in this context.

Major biotechnological applications adopted in recent years are
micro-propagation using tissue culture, biological control of pests,
bio-fertilisers and, most recently, transgenic crops. Plant tissue culture
has succeeded in multiplying propagation materials for agriculture,
horticulture, medicinal, aromatic and forest plants. Biotechnology is also
used for biodiversity conservation - improvement in animal productivity
and health care and aquaculture. Transgenic developments have taken place
in two major areas of crop production: Input and output traits (Hillyer,
1999). Input traits related development is the first wave of biotechnology
evolved to provide a new level of protection against pests and weed
control. Technological developments related to output traits are enabling
crop production with tailored traits that help value additions, such as
high oil content in corn, hybrids with increased levels of amino acids,
healthier oils in soybean, nutraceuticals - blending regular food product
with health enhancing attributes such as golden rice.

However, the application of genetic engineering to agriculture has also
triggered some opposition. The opponents question the safety, relevance
and equity aspects of the technology.

Transgenic or genetically modified (GM) crops have made considerable
progress in many countries. Transgenic soyabean, corn and cotton are being
rapidly adopted in the US, China, Argentina, Australia and South Africa.
The estimated global area of transgenic crops for 2001 is 52.6 million
hectares. Around 5.5 million farmers have adopted transgenic crops.
However, only a quarter of the total adoption has been in the developing
countries

Many other countries have established strong biotechnological research
programmes for various agricultural commodities. In Australia, transgenic
crop was approved in 1997 for Bt cotton. In China, biotechnology research
is being conducted in micro-propagation and varietal improvements of crops
and forestry, diagnosis and control of plant diseases and insect pests,
gene transfer technology of crops and forestry, aquaculture, animal and
veterinary sciences and food sciences.

Socio-economic issues
Suicides among farmers in India are often linked to cultivation of crops,
such as cotton. As these crops are input-intensive, especially with
respect to pesticides, farmers borrow money to meet the costs and in the
event of a crop failure, end up with large debts. A reason often cited as
contributing to such crop failures is resistance build up among the major
pests, such as bollworms and whitefly, to pesticides. Therefore, many
argue that adoption of transgenic crops could help protect the crop
against the most damaging pests and, thus, reduce the risk of crop
failure.

The major change in the cost to the farmers due to transgenic technology
will be that of the seed. This cost is expected to be higher than that of
conventional seed. There could be changes in price of output due to lower
preferences for GM crops in the market, fear of adverse effect on the
health of farm animals, such as cattle and goat, and in the long run
resistance build up

At the society level, the concerns common to biotechnology as such are
effects on the health of human beings, animals, insects and birds, other
plants and, therefore, effect on biodiversity. The standard practice
followed by all countries is to establish biosafety before introducing
this technology.

While the technology may generate large benefits, the question often asked
is how much of it actually goes to consumers and producers. Considering
the structure of the input market and nature of technology, firms may use
monopoly powers to extract rent from farmers.

International experience
Studies have reported that GM cotton, soyabean, and corn varieties have
increased yields and profits and decreased pesticide use of farmers in the
US. The results indicated that farmers gain 43-59 per cent of all rents
created from the introduction and adoption of Bt cotton. The innovators
gain 47-26 per cent of the rent generated. In low infestation years,
however, the innovators got major share in the rent. In Hebei/Shandong
province of China, when farmers bought Bt seeds from the seed companies,
about 83 per cent of benefits went to farmers. The study also found that
farmers with less than one hectare size holdings benefited more (2.35
times) than the farmers with more than one hectare.

The same pattern was observed even if farmers are classified based on
incomes. This pattern may be due to the difficulty encountered by small
farmers in bollworm control. The study found that the insecticide load is
only 10.3 kg/ha in the case of Bt cotton compared to 57.8 kg/ha non-Bi
case. The percentage of farmers reported insecticide poisoning was high in
the case of non-Bt farmers (22.2 per cent) compared to Bt cotton farmers
(4.7 per cent).

India's experience
While biotechnology applications for micro-propagation, biofertilisers,
bio-control agents and animal productivity have already achieved
significant progress, approval on transgenic varieties of crops is still
awaited. Cotton is a major crop of India grown in about 8 million
hectares, highest in the world, accounts for about 20 per cent of the
world acreage. Due to the low productivity of cotton - only 319 kg/ha lint
yield, compared to the world average of 603 kg/ha - India ranks third in
production of cotton.

The losses due to pests are estimated at 10-15 per cent annually. This
necessitates repeated application of insecticides leading to debt and
desperation and sometimes suicides. A study conducted in 1997-98 in
Coimbatore district of Tamil Nadu on the best-bet IRM techniques indicated
that farmers sprayed 9 rounds as against the requirement of 5 rounds and
therefore spent Rs 7184/ha instead of Rs 4177/ha as pesticide cost. A
study conducted during 1995-96 by Insecticide Resistance Action Committee
found that in Guntur district of Andhra Pradesh, the farmers used 21
sprays as against the requirement of 11 sprays and, therefore, spent Rs
6,249 per acre on pesticide application instead of Rs 2,428.

Research on inducing Bt trait in cotton is being conducted by ICAR
research institutions and Mahyco. Mahyco, in collaboration with Monsanto,
has been successful in transferring Bt trait into 40 Indian cotton lines.
The experiment conducted to assess aggressiveness and persistence found
that Bt cotton is not an aggressor on natural flora/habitat. Studies on
toxicity on goats and allergenicity to brown Norway rats found that Bt
cotton is non-toxic and non-allergenic.

In the age of globalisation, not adopting such technology will result in
losses due to lower prices in the market. Such losses could make crop
production non-competitive. To be competitive, it is essential to keep up
with the cutting edge technology.

International experiences have consistently indicated that both yield
increase and cost savings are the major benefits of transgenic crops. The
experience of China is relevant to India as there are similarities with
respect to size of holding and farming practices. The study indicates that
farmer gets more benefit than the seed companies from Bt cotton and more
interestingly small farmers benefit more.

Research indicates that such technology will play a key role in developing
competitiveness of the country for agricultural commodities. In the wake
of the WTO agreement, India cannot afford to lag in adopting safer
technologies. Protecting the livelihood of farmers, equitable growth,
poverty reduction and sustainable production should be the objectives.
(The author is Professor, Centre for Management in Agriculture, IIM,
Ahmedabad.).

**********************************************

Pew Webcast "Labeling GM Foods: Communicating or Creating Confusion?
(Source: foodbiotechnet@listserve.health.org)

Webcast from the Pew Initiative on Food and Biotechnology forum "Labeling
Genetically Modified Foods: Communicating or Creating Confusion?" which
took place on June 27, 2002, in Chicago, IL is now online. The forum
consisted of a panel of speakers representing consumer activists, food
manufacturers, and academics on whether to label "genetically modified"
foods.

You can view the video from the forum at:
http://www.connectlive.com/events/pewagbiotech062702/

**********************************************

IPR Is Not A Constraint To Science

- Crop Biotech Update, July 12, 2002 (Global Knowledge Center on Crop
Biotechnology, International Service for the Acquisition of Agri-biotech
Applications SEAsiaCenter (ISAAA), and CAB International)

"As things stand now, intellectual property does not appear to be the
binding constraint on Southern science. Lack of experience and expertise
in accessing, using, and regulating modern biotechnologies are the real
problems". This is according to a discussion paper entitled "Accessing
Other People's Technology: Do Non-Profit Agencies Need It? How to Obtain
It?" by the International Food Policy Research Institute (IFPRI) authored
by Carol Nottenburg, Philip Pardey and Brian Wright. The article put
special emphasis on agricultural biotechnology and discussed policies of
IPR protection, research exemptions, and the way non-profit institutes fit
in and are at odds with these policies and exemptions.

Intellectual property rights (IPR) were primarily the concern of
inventors, authors, artists and firms that deal in their output. Lately,
public and private non-profit institutions around the world have become
active on the intellectual property scene. For non-profit institutions to
get a return on their investments, they have to sell rights to their
technologies to commercial entities or they may choose to out-license the
technology. As an example, the Association of University Technology
Managers, representing 300 universities, research institutes and teaching
hospitals from the US and Canada, reported over 18,600 licenses active as
of 1999 with an income of $862 million. The authors report that for all
the benefits that non-profit institutions receive from IPR, they are
"neglecting internal monitoring and compliance with respect to other
people's technologies".

It was reported that there are various options for gaining access to IPRs
non-profit agencies are cross licensing, research-only licensing, market
segmentation, mergers or joint ventures, cost-free licensing of
technologies, direct programmatic support from the private sector, patent
pooling, clearinghouse mechanisms, alliance with independent developers of
research tools, and sharing of technology.

Nottenburg is the director of intellectual property at the Center for the
Application of Molecular Biology to International Agriculture in
Australia, Pardey is a Senior Research Fellow at IFPRI, and Wright is a
Professor in the Department of Agriculture and Resource Economics at the
University of California. The paper can be downloaded at
http://www.ifpri.cgiar.org

**********************************************

'Extremely Low' Risk of GM Transfer

- Food Standards Association, July 11, 2002 (From Agnet)
http://www.food.gov.uk/science/sciencetopics/gmfoods/gm_reports

A series of FSA research projects have concluded that it is extremely
unlikely that genes from genetically modified (GM) food can end up in
bacteria in the gut of people who eat them.

The Agencyís independent advisers on genetically modified foods had
expressed concern about the presence of a particular gene (an antibiotic
resistance marker) in GM maize approved for consumption by the European
Community. This led the Agency to commission five related research
projects to investigate the transfer and survival of DNA - the fundamental
genetic material of all living things - in the bacteria of the human gut.

The most recently completed study - which will be published in a
scientific journal later this year - shows that in real-life conditions
with human volunteers, no GM material survived the passage through the
entire human digestive tract. Although some DNA survived in
laboratory-created environments that simulated human or animal
gastrointestinal tracts, the research concluded that the likelihood of
functioning DNA being taken up by bacteria in the human or animal gut is
extremely low.

Much of the work from the first four research projects has already been
published in respected scientific journals. All five reports, including
the study involving human volunteers, can be accessed via the links below.
FSG01007 - Survival of ingested DNA in the gut and the potential for
genetic transformation of resident bacteria G010008 - Evaluating the risks
associated with using GMOs in human foods (Two reports) G01010 -
Assessment of the risks of transferring antibiotic resistance determinants
from transgenic plants to micro-organisms G01011 Dissemination of GM DNA
and antibiotic resistance genes via rumen microorganisms.

These documents are available on the website:
http://www.food.gov.uk/science/sciencetopics/gmfoods/gm_reports

**********************************************

Genetic Improvement: A Review

- consumer_freedom_headlines@orion.sparklist.com

In recognition of the month when America celebrates its freedom, we are
devoting the first two weeks of July to a review of the ongoing battle for
consumer freedom -- the threats and the promise. Today, a review of recent
biotechnology issues.

TRAMPLING THE TRUTH: Anti-biotech activists trampled a field of
genetically improved crops in Scotland in June, while in Rome, Jose Bove,
who led attacks on a field of genetically improved rice and who rallied
radical activists to rip apart a restaurant in 1999, led a mob in calling
for "food sovereignty" and an end to "globalization." But according to
former senators George McGovern and Rudy Boschwitz, "our only hope of
staving off a global pandemic of starvation and chronic hunger in the
first half of this new century is to revive the Green Revolution that
saved an estimated 1 billion lives in Asia, Africa and Latin America in
the '60s and '70s. Thanks to breathtaking advances in high-yield farming,
soil conservation and genetically enhanced seeds, the world has the right
weapons in its humanitarian arsenal÷ Bio-food is the most efficient way of
delivering daily doses of key nutrients and vitamins not found in the
diets of millions of malnourished children and adults÷ The question is not
whether we can afford to make this investment -- the real question should
be whether we can afford not to?"

THE ALTERNATIVE?: Organic crops, on the other hand, will not feed the
world, according to environmental consultant Jim Wells in The Los Angeles
Times: "Organic agriculture is not capable of supplying our country's food
needs while protecting the environment÷ The myths of better nutrition and
eating quality pale in comparison to assertions that organic production
techniques are a viable means of protecting the environment and supplying
the nation's food supply÷ Society will need to depend on modern farming
practices to produce the additional food needed without plowing billions
of acres of wildlife habitat. Only high-yield production agriculture can
accomplish that. When it comes to a healthy, plentiful food supply, modern
farming technology, not organic trendiness, offers the more realistic
solution to feeding a growing world population."

SPEAKING FOR THE STARVING: Kenyan plant pathologist Florence Wambugu
blames starvation in part on "protestors [who] have fanned the flames of
mistrust of genetically modified foods through a campaign of
misinformation," noting: "They can buy their food in supermarkets... They
can choose the more expensive organic foods, or even imported foods. They
can eat fresh, frozen or canned produce. Then, from their world of plenty,
they tell us what we can and cannot feed our children÷ These people and
organizations have become adept at playing on the media's appetite for
controversy to draw attention to their cause. But the real victim in this
controversy is the truth."

**********************************************

Pharm Farming , It's Not Your Father's Agriculture

- Allan S. Felsot, Agricultural and Environmental News, July 2002
(Environmental Toxicologist, Food and Environmental Quality Laboratory,
WSU)

Full Text at
http://www.aenews.wsu.edu/July02AENews/July02AENews.htm#PharmFarming

Imagine a very wealthy country with unsurpassed expertise in discovering
and successfully developing medications that cure some pretty nasty immune
system diseases. Imagine not enough people being able to get the drug
because manufacturers canít make it fast enough. Well, you donít have to
use your imagination because it is happening today in the good old USA.
ìBiotech Industry Squeezed by Lack of ëBreweriesí,î screams a recent
headline in the online version of the San Diego Union-Tribune newspaper.
The article goes on to inform us that demand for protein-based drugs now
on the market far exceeds industryís ability to make enough product.

Before you jump to the conclusion that this is another story concocted by
the evil pharmaceutical companies in an effort to rip off poor,
unsuspecting consumers, letís take a moment and look at how biotechnology
has transformed the manufacturing process.

A Biotech Manufacturing Primer
If you associate pharmaceutical manufacturing with smoke-belching
factories, think again. Many new pharmaceuticals are brewed like fine
wines in fermentation vats lining very clean rooms. The ìvatsî are located
in buildings covering acres of land and plumbed with miles of pipe.
Imagine the energy and controls required to keep the vats humming at just
the right temperature. And thatís just the beginning of the process. The
stuff in the vat, known as the cell culture, has to be piped out and then
extracted in another part of the factory.

As with any manufacturing process, production space is an issue. The cell
cultures used to make the medicinal proteins can only produce so much
during any given timeframe. If a company wants to brew more product, it
needs to add more vats, requiring more space, more energy, and more
personnel. Considering one of these ìnew ageî clean plants costs an
estimated $500 million dollars (Associated Press 2002), one can see why
this industry might be pinched.

A Role for Agriculture
Fortunately for health care consumers, agricultural biotechnology may hold
the solution to the pharmaceutical industryís production problems. Instead
of using gigantic space-gobbling, energy-intensive, expensive factories,
companies are developing the ability to grow medicinal proteins in plants.

This isnít about Uncle Ed putting in a few acres of specially bred plants
out on the north forty. Nor is it about traditional agribusiness growing
food plants containing pharmaceuticals (despite the Internet rumors). A
select elite of meticulous growers will be the new ìgreenî manufacturers
of the next generation of medicinal proteins.

ìPharm farming,î my pet term for the growing of molecules with
pharmaceutical applications in selected crops, is the third wave of
agricultural biotechnology. And it is going to be an ìindustrialî process
without physical walls but with scrupulous controls and regulatory
oversight by at least three Federal agencies.

Riding the Third Wave
The first wave of agricultural biotechnology transformed plants to resists
pests (e.g., Bt-corn and Bt-cotton that contain the insect toxic protein
from Bacillus thuringiensis) or impart resistance to reduced risk
herbicides like glyphosate (e.g., Roundup Ready soybeans). The second wave
involves producing plants with quality-added characters that would
increase agronomic efficiency (e.g., salt-tolerant tomatoes) or
nutritional enhancements (e.g., high-lysine corn). The third wave has been
given the epithet ìplant molecular farmingî and it refers to ìthe
cultivation of plants for industrially, medically, or scientifically
useful biomolecules, rather than for traditional uses of food, feed, or
fibreî (Canadian Food Inspection Service 2001). With the exception of
plant-based manufacturing of the enzyme trypsin (Van Brundt 2002), nothing
has been commercialized at this point, but research and development is
rapidly progressing, especially in the area of human medicines
Proteins, CHOs, and PMPs

The products of pharm farming are called plant-made pharmaceuticals
(PMPs). Presently, the substances under development are proteins with
various functions. Proteins have been used for therapeutic purposes since
the early 1980s when recombinant (i.e., genetically engineered) human
insulin for injection was introduced to treat diabetes. Over the
subsequent years, proteins were discovered with applications ranging from
treatment of cancer and immune system diseases to hemophilia and hormone
deficiencies (Vezina 2001).

The therapeutic proteins are produced in fermentation vats by transferring
their coding genes to cell lines that have the ability to reproduce almost
indefinitely (Figure 1). For example, one of the first commercial PMPs out
of the block will likely be immunoglobulins (Igís), a catch-all term for
different types of naturally occurring antibodies produced by mammalian
plasma cells to ward off pathogens and their toxins. Igís are currently
produced in fermentation cultures of Chinese hamster ovary (CHO) cells.
CHO cells have been around since the late 1950s when they were taken from
the ovaries of adult hamsters and induced to divide and replace themselves
far beyond the typical 50-100 generations of cell cultures at the time.
Today, specialized CHO cell lines can produce a wide variety of human
proteins.

The third wave of agricultural technology has the potential to replace
expensive, energy intensive factories lined with stainless steel
fermentation vats with higher yielding, lower cost, green factories
without walls.

CHO cells are commonly used to manufacture proteins because they divide
rapidly and can be easily transformed to reproduce (i.e., replicate) and
transcribe (i.e., read the code of) DNA from other organisms, including
humans. Igís were particularly challenging because they are actually a
combination of several protein chains that are linked together.
Furthermore, they contain a very large sugar polymer called a glycan.
Thus, Igís are known as glycoproteins. Several genes must work in concert
to produce an intact Ig. However, success in overcoming the complexity of
Ig assembly was reported over ten years ago (Wood et al. 1990). These
early Ig-producing CHO cells could turn out 60 micrograms of antibody per
one million cells every 48 hours.

Unfortunately, with current manufacturing capabilities, CHO cells just
canít keep up with the demand for protein products, especially the Igís.
But over a decade ago, separate tobacco plants were transformed with
mammalian genes that encoded separate component chains of an antibody
(Hiatt et al. 1989). When individual plants containing the different
chains were sexually crossed, the resulting progeny were able to
synthesize a functional antibody. In the mid-1990s, the experiment was
repeated successfully with a different kind of antibody (Ma et al. 1995).
The third wave of agricultural biotechnology was building.

Plants on the Crest
The first wave of agricultural biotechnology showed plants could be easily
and stably transformed with DNA from other species to produce useful
traits that functioned reliably in the environment. So there was no reason
that therapeutic proteins could not be grown in plants, as long as the
genes could be found. While the first wave sought genes from bacteria like
Bacillus thuringiensis (Bt), the therapeutic proteins of the third wave
will require the source codes of human genes. Being proteins, Igís can be
easily grown in plants. The DNA coding sequences that allow CHO cells to
produce Igís can be modified to express well in plants. The plant readable
gene modifications are moved to receptive plants cells along with
accessory DNA pieces to give the plant the capability to start and end the
process of transcribing the gene into its protein product.

Regardless of the nature or function of the protein, the process of
transferring genes from one organism to another and allowing them
functionality is basically the same among different species (see Carpenter
et al. 2002 for an overview of the mechanics of producing
biotechnology-derived crops). The basic technology of plant transformation
has been well studied and commercially implemented in food crops like
corn, soybean, wheat, and canola.

Although the therapeutic proteins can be expressed in any part of a plant,
the goal for PMPs is to express the protein at the highest levels in the
harvestable seed. Seeds are easier and more economical than whole plants
to transport to a processing factory where the proteins can be extracted
and purified in preparation for packaging. Furthermore, under controlled
temperature conditions, seeds can be stored for prolonged periods without
breaking down their protein content. Hundreds of acres of
protein-containing seeds could inexpensively double the production of CHO
cells in a fermentation factory.

As attractive as plants are for turning out great gobs of protein faster,
cheaper, and more efficiently than CHO cells, their use raises all of the
same concerns that have been expressed about the first wave of
biotechnology-derived food crops. In particular, critics worry about
potential gene flow to food crops of the same species, co-mingling of food
and non-food crops, and worker exposure to plant material containing
active pharmaceutical ingredients (APIs). One could argue that the
benefits of pharmaceutical production in plants outweigh the risks, but
industry has wholeheartedly embraced the precautionary principle to ensure
that the risks of the third wave technology are minimized no matter how
great the benefits (BIO 2002). (ED. NOTE: One definition of the
precautionary principle comes from the 1998 Wingspread Conference in
Racine, WI: "When an activity raises threats of harm to human health or
the environment, precautionary measures should be taken even if some cause
and effect relationships ar not fully established scientifically.")

Precautionary Principle at Work
Candidate plants for the production of PMPs will include familiar crops
like alfalfa, canola, corn, potato, rice, safflower, soybean, and tobacco
(BIO 2002). Although the leading candidates for transformation into
workhorses of green manufacturing are familiar food and nonfood crops,
they will be treated altogether differently than the biotechnology-derived
crops designated for food markets. Regulations are swiftly evolving to
ensure the utmost protection of food resources and the environment from
meandering medicines. Specifically, the precautionary principle is hard at
work in several areas to ensure the new technology is low risk and high
benefit.

Current Regulatory Authority
The infrastructure of regulation has been in place for nearly a decade,
and it continues to evolve as experience with biotechnology-derived food
crops grows. Risk management must necessarily focus on providing
protection for human health (worker and consumer) and ecosystems. This
responsibility has been legislatively placed in the hands of four Federal
agencies: USDAís Animal and Plant Health Inspection Service (APHIS), the
Food and Drug Administration (FDA), the Environmental Protection Agency
(EPA), and the Occupational Safety and Health Administration (OSHA).

APHIS and the FDA will stand at the pinnacle of regulation over PMP
production. APHIS will issue permits for growing PMPs during both the
research and development phase and the production phase. Unlike the first
wave crops, pharm crops will need perpetual permitting from APHIS. Permits
for growing small acreages of pharm crops for development purposes are
already being issued, and APHIS has published its mandates for ensuring
maximum environmental protection (USDA-APHIS 2002).

FDA has domain over any products produced by pharm farming. The agencyís
job is to ensure integrity (purity, correct dosages) and safety of the
medicinal product. Before commercial production of the PMPs, FDA will have
already ruled on the safety and efficacy of the pharmaceutical product.
All pharmaceutical risk assessment testing will have to be conducted under
Good Laboratory Practice (GLP) standards, similar to tests required by EPA
for the registration of pesticides. GLP standards subject data to
auditing, guard against fraud, and ensure that all submitted studies can
be reconstructed from scratch.

FDAís responsibility extends to the entire manufacture of the
pharmaceutical, from production to waste streams, so its role necessarily
will complement the role of APHIS because production on the farm will be
the first step in the manufacturing process. To oversee production
practices, FDA has developed regulations called GMPs (Good Manufacturing
Practices), which are the manufacturing analog of GLPs. GMPs ensure
consistent manufacturing processes and product safety, purity, and
potency. As a system that documents practices in all stages of product
manufacturing, GMPs will essentially spread out from its historical
application within the walls of the factory to the wide-open spaces of the
field.

EPA is commonly thought of having its dominion over agriculture through
the regulation of pesticides. EPA would be initially involved in the
regulatory oversight of PMPs if the plants contained pest-protection
characters (like the Bt protein) or herbicide-tolerance characters that
might require a new use pattern for a herbicide, and thus a pesticide
product label change.

EPA also has responsibilities for protection of the environment from
manufacturing processes through application of regulations under the Toxic
Substances Control Act, the Clean Air Act, and the Clean Water Act. Thus,
EPA does have regulatory options should pharm farming raise any
environmental concerns not directly related to pest protection characters
or pesticides. However, many of the environmental issues will have already
been investigated and assessed by FDA as part of the review of
manufacturing processes before full-scale production.

Finally, if worker safety becomes a concern owing to excessive exposure to
PMPs during any stage of production, OSHA has responsibility to require
practices that minimize risk.

Crop Knowledge
Development and subsequent testing of PMPs has proceeded mostly using corn
and tobacco as the green factories. The list of candidate crop plants for
PMP production (i.e., alfalfa, canola, corn, potato, rice, safflower,
soybean, and tobacco) is no accident. In addition to accumulated
experience in using biotechnology to endow these plants with new traits,
mountains of information are known about their physiology and ecology.
Candidate pharmaceutical producing plants have been studied with respect
to pollination, genetics, seed dormancy, and weediness potential. This
information is useful for addressing several concerns, including pollen
movement and subsequent gene flow between conventionally bred and
biotechnology-derived crops. A long history of cultivation shows that the
candidate crops are the least likely to be invasive of ìnaturalî
ecosystems. All of this information will be used to ensure maximal
isolation of the plants from food producing crops.

Principles of Confinement
Long before commercial utilization of crops for synthesis of PMPs,
regulatory agencies will have refined rules for implementing the most
important operating practice for safe manufacturing: the Principles of
Confinement. Confinement essentially means keeping the crop and its
products on the land where it was grown until removed for processing, with
no inadvertent exposure to the public and minimal exposure of products to
workers and the environment. Effectively confined pharm crops will conform
to the following principles that have been elucidated by the biotechnology
companies through the Biotechnology Industry Organization (BIO 2002):

* Prevention of inadvertent human exposure to PMPs through food and feed
* Minimized occupational and environmental exposure to PMPs during ALL
phases of production
* Rigorous compliance with confinement measures
* Analytical methods for detection of expression (i.e., protein) products
* Full cooperation with regulatory reviews of confinement measures and
on-site inspections
* All confinement systems and procedures must be based on sound scientific
principles


Identity Preservation: A Closed Loop System
Preventing co-mingling of pharm crops with food crops will be a prime
directive for industry as well as regulatory agencies. The misadventures
over the co-mingling with food corn of the non-food Bt-corn hybrid known
as StarLinkÆ, which was only registered for animal feed, will not be
repeated. Precaution demands that Standard Operating Practices (SOPs) be
implemented for a functional identity preservation system. Such a system
ensures that the pharm crop is completely segregated from all other crops
and that protocols are in place for production and handling of the crop.
Achieving this goal is possible with implementation of chain-of-custody
procedures that track the product through every stage of production and
processing.

With an effective chain-of-custody program, the crop and its products are
never out of sight. At every step of crop production, commodity
transportation, and product handling, someone acknowledges in writing that
all procedures have been carried out in compliance with the SOPs. In
short, a completely closed loop identity preservation system not only
protects the quality and purity of the final protein product, but it
complements confinement to ensure maximal environmental and worker
protection.