Pharming Cytokines in Transgenic Crops

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Pharming Cytokines in Transgenic Crops

 

Pharming Cytokines in Transgenic Crops

Crop plants are being used to produce a range of vaccines and drugs including

powerful molecules that affect cells of the immune system. The inevitable

contamination of our food crops has been uncovered. Prof. Joe Cummins sounds

warning of cytokines, to be used in agriculture in place of antibiotics.

 

The complete document with references, is available in the ISIS members site.

Full details here

 

Cytokines are small proteins secreted by one animal cell to alter the behavior

of itself or another cell. Cytokines send signals to the cell by binding to

specific ‘receptors’ on the cell-surface. The biological effects depend on the

cytokine and the cell. Typically, these molecules affect cell activation,

division, apoptosis (programmed cell death), or movement. Cytokines produced by

leucocytes and acting mainly on other white blood cells are called interleukins.

Cytokines that have chemo-attractant activity are called chemokines. Those that

cause differentiation and proliferation of stem cells are called

colony-stimulating factors. Those that interfere with viral replication are

called interferons. Interferons protect cells by inducing intracellular

production of molecules that interfere with virus replication, and increase

recognition of virally infected cells by cytotoxic (cell-killing) T lymphocytes.

Interferons also have anti-proliferative effects on some cancer cells.

 

Cytokines provide useful treatments of infections, and of cancer symptoms and

diseases affecting the immune system. Their clinical deployment has been limited

by the cost of producing the drug proteins, and recombinant cytokines have

allowed them to be used more widely.

 

In recent years, animal and human genes have been incorporated into crop plants

in order to produce vaccines, antibodies, plasma proteins, cytokines and other

therapeutics, with little thought given to the consequences of the

pharmaceuticals genes spreading to food crops or the genes and gene products

polluting surface water, groundwater and the air. The first (of possibly many)

such disasters has already been uncovered.

 

It has been suggested that recombinant cytokines might provide a safe

replacement for antibiotics. Chicken interferon gamma has been proposed as a

vaccine adjuvant and growth promoter for chickens. The worldwide production of

chickens for meat and eggs is staggering, so the recombinant interferon

treatment could spread far and wide in short time. To provide for efficient

delivery of the cytokine, adenovirus vectors have been proposed to deliver the

cytokine genes to the chicken. The adenovirus has posed significant problems in

human gene therapy and is known to cause severe immune reactions including

death. The adenovirus may impact the immune system of the treated chicken and

also be carried into eggs, offal and meat. Interferon gamma structural gene has

a high degree of homology (sequence similarity) to human interferon gamma and a

comparison of cytokines in different species shows 6 with 60% or greater

homology to the avian gene and tend to cross react immunologically with the

protein.

 

As a further complication, the cytokine transcript RNA is subject to alternative

splicing to produce different proteins depending on the cellular environment in

which the gene is expressed. This will complicate safety assessment

considerably.

 

Chicken interferon has been produced using baculovirus vector in cultured insect

cells and in transgenic plants both as a source of the cytokine and as a means

of controlling plant disease.

 

Human interferon alpha has been produced in potato and potatoes expressing

interferon alpha were found to resist phytopthora. A ribonuclease gene forming a

part of the human interferon alpha virus defense was used to transform potato,

the transgenic potato ‘defended’ against virus infection by forming necrotic

spots followed by the death of the infected plants 20 days later, a rather

extreme and impractical form of defense.

 

However, production of human interferon in crops may provide therapeutic agents

for a number of human diseases. Oral ingestion of recombinant human interferon

has been reported in over fifty publications involving different disease

treatments, such as the prevention of rejection of allograft islet transplants.

Cytokine treatments are known to induce sickness and central nervous system

toxicity. Recombinant human interferon alpha was reported to cause dementia,

neurotoxicity and mood and cognitive side effects.

 

It is clear that crops expressing interferons would have disastrous consequences

as the interferon genes spread and contaminate food crops, and poison our entire

food chain. Incorporating them into chickens may well produce demented as well

as poisonous chickens.

 

Other cytokines have begun to be produced in crop plants. Interleukin-10 a

powerful immune suppressant used to control graft rejection was produced in open

field trials of modified tobacco. I already warned of the potential for ground

and surface water to become polluted, and the danger that the transgene product,

or the transgene itself could turn a relatively harmless virus into a killer.

The human granculocyte-macrophage colony stimulating factor fused with seed

glutelin protein was used to create an easy system for oral delivery of the

cytokine. Such modified seeds may be widely dispersed by birds and by wind to

contaminate food crops or to propagate the modified crop.

 

Interleukin-2 and interleukin-4 were produced in modified tobacco cells in

suspension culture, the cytokines were excreted into the suspension medium

allowing for easy recovery and purification. This contained production method

should avoid most of the risks of open production in plants in the field.

 

In conclusion, cytokines are proving valuable agents for treating disease, but

like vaccines and other drugs, their production should be confined to contained

facilities, and field releases of any kind should not be allowed.

 

The complete document with references, is available in the ISIS members site.

Full details here

 

 

 

 

 

This article can be found on the I-SIS website at

http://www.i-sis.org.uk/Pharmingcytokines.php

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