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growing cytokines in plants



December 27, 2002
Prof. Joe Cummins
“ Growing cytokines in plants”
Cytokines are small molecular weight messenger proteins secreted by one animal cell to alter the behavior of itself or another cell. Cytokines send intracellular signals by binding to cell surface receptors. Cytokines are produced by most animal cells and have a wide variety of functions. The biological effects depend upon the cytokine and the cell involved, typically these molecules affect cell activation, division, apoptosis ( programmed cell death), or movement. Cytokines produced by leucocytes and effecting mainly 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, they also increase recognition of virally infected cells by cytotoxic T lymphocytes. Interferons also have anti-proliferative functions against some cancer cells. Cytokines provide useful treatments for infection along with along with treatment of cancer symptoms and diseases effecting the immune system . Cytokines proved effective in a wide array of disease treatments but their clinical deployment has been limited by the cost of producing the drug proteins. Recombinant cytokines have allowed a great deal more deployment of the drugs. Molecular farming (pharm crops) in which human or animal cytokines were produced in modified crop plants has been developed in recent years to produce vaccines, antibodies, plasma proteins, cytokines and other therapeutics . However, little thought seems to have been given to the consequences of spread of the modified genes for pharmaceuticals to food crops or to the pollution of surface water, groundwater and to dust and debris from uncontrolled production of the modified crops. Like most of the fruits of genetic engineering production has proceeded with optimism and with little thought to the environmental consequences of the production leading to the first (of possibly many) disasters . Recombinant DNA technology has allowed cytokines to be produced at reduced cost and to provide alternatives for delivery of cytokine genes or their products. It has been suggested that recombinant cytokines might provide a safe replacement for antibiotics. Avian 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 that 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 trauma through the immune system . 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 level of homology with human interferon gamma and a comparison of cytokines in different species shows that genes with 60% or better homology tend to cross react thus the avian interferon may carry over into eggs, offal and meat and cross react with mammals. As a further complication cytokine gene messenger RNA have been to found to be spliced in alternative ways meaning that the gene may produce different proteins depending on the cellular environment in which the gene is activated . Safety evaluation of the treated animals will have to experimentally evaluate
the products , not just assume that they are substantially equivalent.
Interferon has been produced in baculovirus effecting insects 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 bearing 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 . The transgenic plant defense seems rather extreme and impractical. However, production of human interferon in crops may provide a therapy 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 causes dementia , it also causes neurotoxicity and mood and cognitive side effects . Spread of crop genes bearing interferon would have disastrous consequences . Of course, a demented chicken may not be a serious problem until after you have consumed it (or it has consumed you)! Other cytokines have begun to be produced in crop plants. Interleukin-10 a powerful immune suppressing product used to control graft rejection was produced in open field trials of modified tobacco(. The potential for ground and surface water pollution along with the possible danger of interaction between the transgene and virus was discussed along with the fundamental danger of secret field trials and contamination of food crops. 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 . Human granculocyte-macrophage colony stimulating factor was fused with seed glutelin protein to create an easy system for oral delivery of the cytokine . In conclusion, cytokines are proving valuable agents for treating disease, care must be given to insure that food crops and the environment are not polluted with the products. The most pressing immediate issue is the need to insure that the public be informed about the nature and location of open field trials and production facilities for the crops modified with cytokine genes. In North America extensive environmental releases of such modified crops have been undertaken in a climate of secrecy that threatens all farmers but particularly organic farmers and the general public. Field releases of any kind should not be allowed because testing production can be achieved in cell culture or contained facilities.

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