[Date Prev][Date Next][Thread Prev][Thread Next][Date Index][Thread Index]
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.
.