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Eat up your Vaccines. without us even knowing.

 

 

 

 

 

 

 

Eat up your vaccines

 

Edible vaccines are being touted by the agbiotech industry as an example of

the benefits genetic engineering can bring to the South. Claims that they

will be cheap, accessible and safe, and eliminate the need for the dreaded

needle, sound like a dream come true. But the vaccine in a banana is still

far from reality, and we will all likely be a lot better off without

itanyway.

 

Genetic Resources Action International (GRAIN)

 

_____

 

NOT only have the first generation of genetically modified (GM) crops been

disappointing in terms of their agronomic and economic returns, they have

been a spectacular failure in terms of generating public support for GM

foods. In many countries, the spread of GM crops has largely come to a

standstill. As a result, the agbiotech industry has changed direction and is

hoping to win the public over with its new collection of designer crops.

 

Unlike the first generation, which supposedly delivered benefits for the

producer, the second-generation crops will - we are promised - be designed

with the consumer in mind.

 

The second generation is focusing on what are known as 'functional foods'.

Broadly defined, these are products with a claimed consumer benefit, such as

taste, nutritional value, or as a drug delivery system. Functional foods,

such as chocolate bars with ginseng, are already widely available in Europe

and the US. To date, the extra 'function' has been added during processing,

rather than as a result of genetic manipulation, but this is set to change

shortly. All the major agbiotech giants - such as Syngenta (the agribusiness

company formed in November 2000 from the merger of Novartis Agribusiness and

Zeneca Agrochemicals), Monsanto and Aventis - are investing heavily in

functional foods. Their agenda is clear. Daniel Vasella, chairman and CEO of

Novartis, echoes the hopes of the whole industry in his belief that

'tangible consumer benefits could turn the debate on genetically modified

food.'

 

Some of the more ambitious functional foods in the pipeline are those with

pharmaceutical applications. A growing number of companies are starting to

engineer plants to produce therapeutic proteins to be used as drugs and

vaccines. Up to now, mammalian and microbial cell cultures have been used as

'bioreactors' to produce these therapeutic proteins, which generate more

than US$18 billion in combined sales per year, a figure projected to

increase by 20-30% this decade.

 

The attraction of plant-based systems is that they exhibit good genetic

stability, and are cheaper to develop and easier to scale up for commercial

production. The US-based company Epicyte Pharmaceutical has a number of

'plantibodies' (proprietary technologies for producing antibodies in plants)

in clinical development. CropTech corporation is genetically modifying

tobacco to produce therapeutic proteins and Large-Scale Biology is working

on a non-Hodgkin's lymphoma vaccine. Planet Biology is conducting clinical

trials on a monoclonal antibody produced in GM plants that prevents the oral

bacterial infection that contributes to tooth decay.

 

Edible vaccines

 

Of all the work on functional foods, research into edible vaccines has

captured the public's imagination the most. 'One day children may get

immunised by munching on foods instead of enduring shots,' suggests

Scientific American magazine. 'More important, food vaccines might save

millions who now die for lack of access to traditional inoculants.'

 

Edible vaccines are the latest, greatest hope of the floundering biotech

industry, along with Vitamin A or 'golden' rice, to convince a sceptical

public that genetic engineering will help the hungry and sick in the South

as well as the North. Foods under study as edible vaccines include bananas,

potatoes, tomatoes, lettuce, rice, wheat, soybeans and corn. The media have

delighted in conjuring up images of African families venturing no further

than their garden to pluck a vaccine-laden banana from their homegrown tree

to protect them from the major killer diseases of the day. Hoechst's

in-house magazine, Future, says that 'We may some day think that getting a

shot against hepatitis is a rather primitive, old-fashioned way to

administer a vaccine.'

 

The advantages, says Scientific American, 'would be enormous. The plants

could be grown locally, and cheaply, using the standard growing methods of a

given region. Because many good plants can be regenerated readily, the crops

could potentially be produced indefinitely without the growers having to

purchase more seeds or plants year after year. Homegrown vaccines would also

avoid the logistical and economic problems posed by having to transport

traditional preparations over long distances, keeping them cold en route and

at their destination. And, being edible, the vaccines would require no

syringes - which, aside from costing something, can lead to infections if

they become contaminated.'

 

Medicine's Holy Grail

 

Vaccination is one of the medical world's greatest success stories.

 

'Vaccines have accomplished near miracles in the fight against infectious

disease,' proclaims Scientific American. Between 1970 and the late 1990s, an

international campaign to immunise all the world's children against six

devastating diseases (diphtheria, whooping cough, polio, measles, tetanus

and tuberculosis) increased the number of infants vaccinated from 5% to

about 80%, and reduced the annual death toll from those infections by

roughly three million. But, vaccine proponents argue, the 20% of infants

still missed by the six vaccines account for about two million unnecessary

deaths each year, especially in the most remote and impoverished parts of

the globe. Regions harbouring infections that have faded from other areas

are like bombs ready to explode, and international travel and trade increase

the mobility of infectious diseases. 'Until everyone has routine access to

vaccines, no one will be entirely safe,' warns Scientific American.

 

The World Health Organisation (WHO) has called for new strategies to deliver

vaccines to reach the populations that existing programmes have failed to

reach. Existing vaccines are expensive, need refrigeration and require a

skilled person to give the injection - with needles that are hard to come by

in some places. Hence the appeal of edible vaccines. But just how realistic

or desirable is the dream of the backyard vaccine banana?

 

Backyard bounty

 

Appealing as it is, reality will probably fall short of the backyard banana

tree. 'Our main worry with this technology is the dosage,' says Bernard

Ivanoff, global coordinator for vaccines at the WHO. In determining the

right dosage, the patients' weight and age need to be considered, as would

the size and even ripeness of the banana. Charles Arntzen, one of the

pioneers of edible vaccines, acknowledges the challenge of assessing how

much an infant, in particular, ingests. 'A baby may eat a bite and not want

any more, may spit up half of it, or eat it all and throw it up later,' he

concedes.

 

Researchers are now recognising that edible vaccines would be unlikely to

make the role of the vaccine provider redundant, and that attempting to

concentrate the vaccine into a teaspoon of baby food would be more practical

than administering a whole banana. This, then, begs the question: why bother

to engineer it into a banana in the first place?

 

Big task for a banana

 

Because heat denatures (inactivates) vaccines, the food material being

engineered to produce the vaccine will have to be eaten raw. Many current

studies focus on engineering vaccines into potatoes - the potato can

attribute its current popularity to the fact that it is easy to engineer -

but it is generally recognised that the potato is unlikely to be a popular

or practical vehicle.

 

Bananas are being eyed as the vehicle of choice, particularly for Third

World applications, because of their worldwide popularity, abundance and

baby-friendliness. But bananas have their own problems. They contain very

little protein, so they are unlikely to produce large amounts of recombinant

proteins (i.e., vaccines). Banana trees also take a few years to mature and

the fruit spoils fairly rapidly after ripening, making transportation and

storage difficult. Researchers at Cornell University in the US have so far

been unsuccessful in their attempts to engineer a vaccine into a banana

plant. Even if they can be tweaked to produce viable amounts of vaccine, it

is well known that plants don't grow very well when they are producing large

amounts of foreign protein. The GM potatoes used in Cornell's human trials

were small - about the size of a thumb.

 

Transportation

 

One of the big draws for edible vaccines is the potential to drastically

reduce or eliminate transport costs. But the impracticality of the backyard

banana means that the elimination of transport costs is not a realistic

scenario. Some researchers imagine vaccines being produced in national or

regional greenhouses, which would be an improvement on flying the vaccines

in from overseas, but this could probably better be achieved by establishing

a conventional vaccine plant in-country. The environmental and ecological

risks posed by edible vaccines (see below) also make it questionable whether

many countries in the South should be expected to have the facilities and

expertise available to grow the vaccines safely and successfully.

 

Needle-free shots

 

Another much-hyped advantage ignores the fact that if they could be given

orally, today's vaccines already would be. Few vaccines are absorbed well

from the gut because they are too big to cross the gut wall easily and/or

are broken down by the gut enzymes. Edible vaccines would be subject to the

same limitations as any other oral drugs.

 

Cheap, cheap, cheap?

 

One of the key goals of the edible-vaccine pioneers is to reduce

immunisation costs. The theory goes that edible vaccines would be far

cheaper than current injectable vaccines since they would not have to

undergo the expensive purification and refrigeration of traditional

vaccines, and shipping costs would be much reduced. As we have seen,

shipping costs may not necessarily be significantly reduced, and edible

vaccines may still require refrigeration. Even if edible vaccines are

cheaper, it is not clear that this will lead to increased vaccination

coverage, since the cost of the vaccine is a small part of the whole

package. According to the WHO, to immunise a child costs no more than $1 for

the big six vaccines, but $14 for programme costs (laboratories, transport,

cold chain, personnel and research). For the newer, more expensive vaccines,

such as hepatitis B and AIDS, the cost of the vaccine plays a more

significant role, but the nature of the vehicle (banana or syringe) will

still only represent a small part of the total cost.

 

Will they work?

 

Research into edible vaccines is still at a very early stage and they have a

long way to go in proving their efficacy. Getting plants to express adequate

amounts of the vaccine is proving challenging enough, let alone translating

that into an appropriate immunological response in people. Producing stable

and reliable amounts of vaccines in plants is complicated by the fact that

tomatoes and bananas don't come in standard sizes. There may also be

side-effects due to the interaction between the vaccine and the vehicle. In

many countries in the South, stringent quality control standards for

standard drugs are quite a luxury, let alone dealing with the added

complications posed by edible vaccines. People could ingest too much of the

vaccine, which could be toxic, or too little, which could lead to disease

outbreaks among populations believed to be immune.

 

Oral vaccines are also more difficult to formulate than injectables - for

example, the oral polio vaccine is more convenient but less effective than

the injectable one. The vaccines are likely to need cofactors (adjuvants)

such as cholera toxin to enhance their uptake and increase their

effectiveness. In addition, new vaccines have to be tested worldwide, since

their effectiveness is not uniform in different contexts. When the

tuberculosis vaccine (BCG) was tested in the UK, it proved to be effective.

 

But it did not work in India, probably because tuberculosis is linked to

nutritional status.

 

Environmental and health risks

 

Over the last two decades, there has been a dramatic increase in outbreaks

of new and re-emerging infectious diseases. One of the factors implicated in

this phenomenon is the transfer of genes across unrelated species of animals

and plants. This 'horizontal gene transfer' has been pinpointed as being

responsible for the new bacterial strains involved in the cholera outbreak

in India in 1992 and the Streptococcus epidemic in the UK in 1993.

 

Antibiotics and traditional vaccines already contribute to horizontal gene

transfer. Recombinant vaccines, like those that would be used in edible

vaccines, would exacerbate such transfer. This is a serious concern for the

release of any genetically manipulated organism, but particularly worrisome

in the case of vaccines, because of their disease-causing potential.

 

The ecological and environmental risks of edible vaccines seem to have

received little attention, despite the fact that they present major hazards

(see box). Containing these risks, assuming they are taken seriously, would

certainly eliminate the possibility of the backyard banana, and greenhouse

facilities would need to be rigidly controlled. The risks associated with

edible vaccines are particularly worrisome given the medical community's

blind faith in vaccination in general and its seeming unwillingness to take

seriously evidence that has been accumulating related to vaccine safety

(such as the rise of autoimmune diseases).

 

Regulators are trying to figure out how to deal with plants engineered to

produce drugs. Some safeguards are already in place. In the US, all field

tests of drug-producing plants require government permits, while some field

tests of other modified crops require only notification of the relevant

government body. For no particular sound scientific reason, the required

distance by which the drug-bearing plants must be isolated from other plants

to prevent cross-pollination has been set at double the usual distance. But,

as with releases of all genetically modified organisms (GMOs), the

parameters considered in determining a product's 'safety' are extremely

limited, and do not inspire confidence in dealing with the many and varied

risks associated with edible vaccines.

 

Vaccine movers and shakers

 

Much research on edible vaccines is being undertaken in the public sector at

present (see box). The industry is eager to hype up the benefits of edible

vaccines to win over support for genetic engineering, but this seems to be

more of a public relations exercise than real commitment. As indicated by

the roster of patent applications on edible vaccines ( table not included),

most industry research is being undertaken by small technology companies,

rather than the big vaccine producers. A few large companies, like Mycogen

(Dow Agrosciences), are looking into edible vaccines, but are more

interested in the livestock market than human application.

 

Cornell University's of Cornell's Charles Arntzen, who pioneered the idea of

edible vaccines, says he has had little success in selling the idea of

edible vaccines to the big vaccine producers. He sees two main reasons for

this. Firstly, his main focus has been on vaccines for the South, such as

diarrhoeal vaccines, which are not seen as a good investment by the

companies. Secondly, they 'have the market sewn up with traditional

injections'. Arntzen believes that a small vaccine start-up will have to

lead the way in proving the viability of the technology, and that the big

companies will follow.

 

Historically, profit margins in vaccine markets have been low as compared to

pharmaceutical markets primarily due to the non-proprietary nature of common

vaccines. In the 1970s and 1980s, innovation was slowed by the paucity of

resources and competition in this area, primarily due to concerns of

liability and commercial viability. In the US, legislation in the last 10

years that removed liability from companies except in relation to

manufacturing defects has encouraged re-entry into the market. Vaccine

companies are reaping bigger profits again. The world vaccine market was

estimated to be $3.6 billion in 1999 and is growing at 12% annually.

 

The market is highly concentrated, with three pharmaceutical giants

(SmithKline Beecham, Aventis [which has swallowed up both Merck and Pasteur

Connaught Merieux] and Wyeth Lederle) accounting for more than 75% of sales.

 

The advent of recombinant vaccines, which are being developed against

malaria, AIDS and hepatitis B, means that vaccines are no longer necessarily

cheap. When it first came on the market in the US, the hepatitis B vaccine

cost $150 a shot. Although the price has now come down to $1, it is still

well out of the range of affordability in developing countries. Some

researchers point to these new recombinant vaccines as possible candidates

for edible vaccines: the injectable vaccines against diphtheria, tetanus,

pertussis, and so on are so cheap now that there would be little incentive

to develop edible vaccines for them. But it is just these technologies that

the corporations would be hugging tightly to their chests for as long as

their patents will allow.

 

Vaccine companies are only interested in developing vaccines that will sell

in the North. As HIV vaccine developer Stanley Plotkin of Aventis Pasteur

explains, 'The keystone of the [global vaccination] system is that the

research costs are recouped in North America and Europe, and the vaccines

are sold in the developing world at much, much lower margins.' Hence, very

little research is undertaken on diseases that have no market in the North.

 

According to the World Bank, funds for global public and non-profit malaria

research in 1993 totalled about $84 million, with only a small part of that

devoted to vaccine research. The amount of private sector spending is

'generally considered to be even smaller.' Because of this, the World Bank

is looking into setting up a $1 billion fund to help countries purchase

vaccines. Such a fund could 'ensure that there would be a market for

malaria, tuberculosis or AIDS vaccines if they were developed, and thus

would create incentives for vaccine research.'

 

How effective the establishment of such a fund would be in stimulating

research in the industry remains to be seen, but it would no doubt be

welcomed by the agencies involved in vaccination programmes in the South,

such as the United Nations Children's Fund (UNICEF) and the WHO.

 

In terms of the potential of edible vaccines, the WHO is cautiously

optimistic.

 

According to the WHO's Uli Fruth, the 'WHO is very interested in

technologies which (a) may render vaccines more affordable for use in

developing countries, (b) may allow future vaccine production in developing

countries and © can be delivered needle-free. All three conditions appear

to be fulfilled in this case.' The WHO is not investing heavily in

edible-vaccine research, but has provided some seed-funding (Arntzen's work

on edible vaccines at Cornell) to help establish proof of principle. Fruth

acknowledges that before endorsing such vaccines for human use, the WHO's

concerns related to quality assurance, efficacy and environmental impact

will need to be addressed in a satisfactory fashion. But if the WHO's

position on GM foods is anything to go by, its approach to safety issues is

unlikely to be very wide-reaching or reassuring. A joint WHO/FAO

consultation on the safety of GM foods recently concluded that the

pre-marketing safety assessment [of GM foods] already gives assurance that

the food is as safe as its conventional counterparts.'

 

Just a pipe dream?

 

Despite their willingness to present edible vaccines as an example of the

benefits of GM foods, the pharmaceutical and agbiotech industries seem to be

merely tinkering with the idea at the moment, and are not investing heavily

in research. A few small biotech companies and university departments are

pioneering the way. It is possible that in time they may convince the

corporate giants to let go of their established technology and invest in

edible vaccines, but this seems unlikely given the complexity of the

challenge of creating a safe, convenient and affordable product. People all

over the world can breathe a big sigh of relief (at least for now), given

the serious risks that edible vaccines pose. As Norway's biosafety expert

Terje Traavik has pointed out, 'there is a most striking lack of holistic

and ecological thinking with regard to vaccine risks. This seems to be

symptomatic of the real lack of touch between research in medicine and

molecular biology on one hand, and potential ecological and environmental

effects of these activities on the other.'

 

The potential for harm that edible vaccines pose highlights the need for

thorough and wide-reaching risk assessments for GMO releases.

 

Current frameworks for regulation are woefully inadequate. In addition,

researchers and policy makers need to examine closely the whole field of

infectious diseases. There are other ways of preventing the spread of

infectious diseases (such as breaking transmission chains) and these must be

given greater attention instead of focusing solely on the technofix solution

of vaccination. This does not necessarily mean abandoning vaccination

altogether, but developing a more holistic approach to the management of

infectious diseases.

 

Genetic Resources Action International (GRAIN) <www.grain.org

<http://www.grain.org%20%3Chttp:/www.grain.org> <http://www.grain.org>> is

an international non-governmental organisation promoting the sustainable

management and use of agricultural biodiversity based on people's control

over genetic resources and local knowledge, with a special emphasis on

developing countries. The above article first appeared in GRAIN' quarterly

newsletter, Seedling (December 2000).

 

Main Sources

 

*WH Langridge (2000), 'Edible Vaccines' Scientific American, September 2000.

 

*T Traavik (1999), 'Environmental Effects of Genetically Engineered

 

Vaccines,'hird World Network Online,

<http://www.twnside.org.sg/title/vaccine.htm>

 

*Mae-Wan Ho et al (1999), 'Sowing Diseases, New and Old', Third World

Network Online, <http://www.twnside.org.sg/title/heal-cn.htm>

 

*M Hansen (1999), 'Gnetic Engineering is Not an Extension of Conventional

Plant Breeding,'Consumer Policy Institute,

<http://www.consumersunion.org/food/widecpi200.htm>

 

*R Glennerster and M Kremer (2000), 'A World Bank Vaccine Commitment'

Brookings Policy Brief #57, May 2000.

 

*'Safety Aspects of Genetically Modified Foods of Plant Origin', Report of a

Joint FAO/WHO Expert Consultation on Foods Derived from Biotechnology, WHO,

Geneva 2000. WHO and UNICEF (1996), The State of the World's Vaccines and

Immunisation, <http://www.unicef.org/newsline/vpressr.htm>

 

*V Griffith (2000) 'Fighting Disease with Edible Vaccines,' Future (Hoechst

in-house

magazine),http://www.archive.hoechst.com/english-3er/publikationen/future/er

naehr/art3.htm

 

*A Pollack (2000), 'Ventures Aim to Put Farms in Pharmaceutical Vanguard,'

New York Times, 14 May 2000.

 

*J Toonen (1996), 'Seeds of a New Medicine,' Biotechnology and Development

Monitor No.27, pp 12-14,

<http://www.gene.ch/www/pscw.uva.nl/monitor/2707.htm>

 

.. Wilkins (1999), 'Edible Vaccines I'll Take Mine With a Grain of

Salt,' Biotech Times Vol.5, No.2.

 

*Personal communication with Charles Arntzen, Arizona State University; Uli

Fruth, Vaccines and Biologicals, WHO; and Ted McKinney, Mycogen.

 

 

 

Box stories

 

 

Who is doing what with edible vaccines?

 

.. The first human clinical trial of an edible vaccine took place in

1997, when volunteers ate raw potatoes genetically engineered against

diarrhoea-causing E coli. Ten of the 11 volunteers who received the vaccine

had fourfold rises in serum antibodies.

 

.. Researchers from the Boyce Thompson Institute (BTI) at Cornell

University conducted another clinical trial of an edible vaccine in 1999.

Potatoes containing the Norwalk virus (which causes vomiting and diarrhoea)

fed to volunteers elicited an immune response in 19 out of 20 subjects. BTI

researchers are attempting to engineer vaccines into bananas and have

produced powdered tomatoes that carry Norwalk virus DNA. BTI scientists have

also been awarded a Rockefeller Foundation grant - $58,000 for three years -

to collaborate with Mexican researchers at the Mexican health agency,

CINESTAV.

 

.. Prodigene and Stauffer Seeds (a spin-off of Staffer Chemical,

formerly a division of Novartis) have conducted clinical trials on pigs

using an edible vaccine for transmissible gastroenteritis virus (TGEV)

expressed in corn, and are developing a Hepatitis B vaccine for humans.

 

.. The US' Large Scale Biology Corporation is developing a

patient-specific non-Hodgkin's lymphoma vaccine in plants. Current methods

for making the custom vaccine require up to a year to produce vaccine for

patient use; LSB thinks its production process could reduce that time to 6-8

weeks.

 

.. Under license from Mycogen, the UK's Axis Genetics was developing

an oral hepatitis B booster vaccine in edible plants, and had plans for

Norwalk virus and diarrhoea. Axis went out of business in 2000, saying that

protests over bioengineered food had scared off investors. Myocgen continues

to work on edible vaccines for animals.

 

.. Under license from Groupe Limagrain, Meristem Therapeutics has

developed industrial processes for the large-scale production of recombinant

therapeutic proteins in plants. Plants including tobacco, corn, potato and

rape seed are being used as bioreactors for the production of enzymes,

antibodies, and vaccines.

 

.. The Scripps Research Institute is working on an edible HIV vaccine.

 

Initial success has been reported in splicing amino acids from HIV into the

cowpea mosaic virus (CPMV). When inoculated with CPMV, cowpea plants

reproduce HIV.

 

.. Scientists in Poland working with the US' Thomas Jefferson

University have tested a hepatitis B vaccine contained in lettuce on human

subjects.

 

.. In Melbourne, Australia, CSIRO has grown a measles-fighting tobacco

plant and has begun pilot studies with oral plant-based vaccines for malaria

and HIV.

 

 

 

 

Genes going wild

 

Genetic engineering is inherently hazardous because it depends on developing

gene transfer vectors (carriers) specifically designed to cross wide species

barriers. It promotes the transfer of genes horizontally across species,

instead of vertically within species by inheritance. It is also increasingly

designed to overcome the species' defence mechanisms which degrade or

inactivate foreign genes. It is still a very crude science, with genes being

inserted at random points in the host's genetic material (genome), rather

than being carefully pinpointed as happens in traditional breeding. For

these and other reasons, genetic engineering destabilises the genomes of its

plant and animal hosts, and the effects ricochet through the neighbouring

ecosystem. There is growing evidence that by facilitating horizontal gene

transfer and recombination, genetic engineering may be contributing to the

emergence and re-emergence of infectious, drug-resistant diseases.

 

Edible vaccines (even subunit vaccines) will always entail the ingestion of

recombinant viral genetic material, and hence pose considerable risks to the

environment and health. Edible subunit vaccines are likely to be less

dangerous than those that may be produced using genetically modified viruses

and viruses used as vectors (carriers) for the vaccine. But they still

involve the insertion of foreign genes into the plants and the implications

thereof. Genetically tweaking the pathogen to reduce its potency is even

more risky. It has been demonstrated that minor genetic changes in, or

differences between, viruses can result in dramatic changes in host spectrum

and disease-causing potentials. According to Terje Traavik of the Norwegian

Institute of Gene Ecology, 'For all these vaccines, important questions

concerning effects on species other than the targeted one are left

unanswered so far.' There are also considerable risks related to the

possibility of a genetically engineered vaccine virus engaging in

recombinations with naturally-occurring relatives. New viruses resulting

from such events 'may have totally unpredictable characteristics with regard

to host preferences and disease-causing potential,' says Traavik.

 

Naked DNA vaccines, which comprise the genes of the pathogen without the

virus 'shell,' are perhaps the most risky. These short pieces of DNA are

readily taken up by cells of all species, and may become integrated into the

cell's genetic material. Unlike chemical pollutants which dilute out and

degrade over time, these small DNA fragments can be taken up by cells and

multiply and mutate indefinitely. They are known to have significant and

harmful biological effects, including cancers in mammals. Upon release or

escape to the wrong place at the wrong time, horizontal gene transfer with

unpredictable biological and ecological effects is a very serious, and as

yet unregulated, hazard.

 

Sources: T Traavik (1999), 'Environmental Effects of Genetically Engineered

Vaccines,' Third World Network Online,

 

<http://www.twnside.org.sg/title/vaccine.htm>; Mae-Wan Ho et al (1999),

 

'Unregulated Hazards of Naked and Free Nucleic Acids', ISIS report for the

Third World Network. <http://www.i-sis.org/naked.shtml>

 

 

 

 

How vaccines work

 

Vaccines work by priming the immune system to swiftly destroy specific

disease-causing agents before they can multiply enough to cause symptoms. To

date, this priming has been achieved by presenting the immune system with

whole viruses or bacteria that have been killed or 'attenuated' (made too

weak to proliferate much). The immune system responds to this vaccine as if

it were under attack by a fully potent antagonist and mobilises its forces

to destroy the foreign body. Memory cells are then left behind on alert,

ready to unleash whole armies of defenders if the real pathogen ever finds

its way into the body.

 

Classic vaccines pose a small risk in that the killed or attenuated

microorganism can sometimes spring back to life, causing the disease they

were meant to prevent. For this reason, 'subunit' vaccines (which contain no

genes, just proteins derived from them) are now favoured, since they reduce

this risk. They are, however, often not as effective as live vaccines.

 

Subunit vaccines are also expensive, because they are produced in cultures

of bacteria or animal cells and have to be purified and refrigerated.

 

Many researchers hope that they will be able to develop edible vaccines

which are similar to subunit preparations, containing only the genes coding

for certain antigens, not the whole virus or bacterium. One of the main

hurdles to be overcome here is that the antigens could be degraded in the

stomach before having time to act. (Typical subunit vaccines have to be

delivered by injection precisely because of this). Researchers working on an

edible hepatitis B vaccine suggest that oral doses may need to be 10-100

times higher than the injectable dose to elicit a comparable immune

response.

 

Source: WH Langridge (2000), 'Edible Vaccines', Scientific American,

September

 

 

 

 

 

 

Edible vaccines

 

Professor Joe Cummins points out the risks of edible vaccines now under

development in a variety of common food plants.

 

IN the early 1980s, the World Health Organisation called for oral vaccines

that do not need refrigeration and are inexpensive to produce.

 

Such vaccines, it was believed, would eradicate most infectious diseases

worldwide.

 

During the past 10 years, crop genetic modification has been investigated as

a means of making edible vaccines that could be produced locally without

refrigeration. Food vaccines have been developed using bananas, potatoes and

tomatoes, as well as lettuce, rice, wheat, soybeans and corn. Corn and

alfalfa have been developed to provide vaccines for farm animals. For the

most part, the vaccines are developed using selected proteins from the virus

or bacterium being protected against. In some instances, plant viruses such

as alfalfa mosaic virus or tobacco mosaic virus are modified to produce

antigens (proteins eliciting immune reaction) of mammalian virus or

bacterial disease. The modified plant viruses rapidly produce high levels of

antigens for oral immunisation against mammalian viruses or bacterial

pathogens [1]. Many edible vaccines are poised for release and clinical

trial, even though numerous important questions remain unsolved.

 

One complication with oral vaccines is 'oral tolerance'. When antigens are

taken up in food repeatedly, the production of antibody in the immune

response may be suppressed. In autoimmune diseases such as arthritis,

diabetes and multiple sclerosis, antigens are produced in tissues which are

attacked by the body's own immune response. When quantities of the target

antigen, such as collagen in arthritis, are eaten, the autoimmune disease is

suppressed, and many patients experience relief. Indeed, antigens for

autoimmune disease are being introduced into crop plants to treat the

symptoms of autoimmune disease. For the same reason, however, oral vaccines

in food may lead to undesirable suppression of immunity to the disease

normally protected by the vaccine [1,2].

 

Food crops containing vaccines may readily contaminate crops that are used

as food. This point has been made previously [3]. For example, it is assumed

that potatoes do not spread by pollination or by over-wintering tubers.

 

Actually, both modes of transfer are known. Genes for the vaccines may also

spread horizontally by sucking insects and by transfer to soil microbes. The

genes and proteins may be released during plant wounding or breakdown of

roots and rootlets and pollute surface and ground water. The vaccines may

provoke allergic responses if humans or other mammals or birds are

repeatedly exposed to the allergen.

 

In addition, many instances of recombination between viral transgenes and

viruses have already been reported (reviewed in [4]). Have these plants been

assessed for their ability to generate recombinant viruses? When genes of

viruses infecting human beings are incorporated into plants, are we not

increasing the potential for generating new recombinant viruses that may

cross from plants to human beings?

 

The crops modified to produce edible vaccines should be scrupulously

maintained for that purpose alone. Recently corn modified as an edible

vaccine for a swine virus was promoted by the company inventing it. It was

promised that the genetically modified (GM) corn would be grown under

'rigorously controlled conditions, and used only for the expressed purpose

of vaccine production' [5]. Such a commitment is essential but such promises

should be viewed in the light of StarLink corn that was approved only for

animal consumption but appeared in foods for human consumption.

 

GM crops as edible vaccines should be restricted to plant tissue culture or

to contained plant growth chambers or high-security greenhouses. During

epidemics such as the foot-and-mouth disease outbreak, there is likely to be

pressure to widely grow GM alfalfa modified with foot-and-mouth virus

structural proteins [6]. However, widespread and prolonged exposure to the

virus antigens is likely to defeat the purpose of the vaccine. There is also

the risk of creating new strains of foot-and-mouth virus as well as viruses

that cross between plant and animal kingdoms [3].

 

In conclusion, edible vaccines made up of GM crops modified with genes from

disease organisms are inexpensive to produce and do not need refrigeration.

 

However, careless releases of GM vaccine crops to the environment and

general food supply are likely to produce undesirable side-effects such as

greater disease impact or allergy to the food. Edible vaccines in GM crops

should be strictly confined to laboratory tissue culture, growth chambers or

greenhouses.

 

1. Landridge,W. (2000). 'Edible Vaccines'. Scientific American online,

September.

 

2. Weiner, H. (1997). 'Oral tolerance for treatment of autoimmune

diseases'. Ann Rev Med 48,341-51.

 

3. Ho, M. W. and Steinbrecher, R. (1998). 'Fatal Flaws in Food Safety

Assessment'. Environmental & Nutritional Interactions 2, 51-84

 

4. Ho, M. W., Ryan, A. and Cummins, J. (2000). 'Hazards of transgenic

plants with the cauliflower mosaic viral promoter'. Microbial Ecology I in

Health and Disease 12, 6-11.

 

5. 'Edible Vaccine Success'. In Brief, Nature Biotechnology 18,367,2000.

 

6. Wigdorovitz, A., Carrillo, C., Dus Santos, M., Trono, K., Peralta, A.,

Gomez, M., Rios, R., Franzone, P., Sadir, A., Escribano, J. and Borca,M.

(1999). 'Induction of a protective antibody response to foot and mouth

disease virus in mice following oral or parenteral immunisation with alfalfa

transgenic plants expressing the viral structural protein VP1'. Virology

255,347-53.