by Prof. Edward J.B. Kakonge
Biochemist Department, Makerere University

Genetic Modification
Genetic modification of living organisms has been going on for millions of years, but at a very slow imperceptible pace. Much of our agriculture and animal hus-bandry is based on selecting desirable characteristics in plants or animals and preserving and propagating these characteristics.

The animal and plant breeders are always on the lookout for desirable characteristics in animals and plants to preserve and propagate. The propagation of desirable characteristics involve Genetic Modification. The desirable characteristics which the breeders select are determined by GENES. The process of propagating these characteristics involves gene exchange between one organism and another. This process involves whole exchange of genes which determine desirable and undesirable characteristics and create new varieties or breeds. With the development of Biochemistry, the study of inheritable characteristics and Molecular Biology has led to a better understanding of the chemical composition of genes including those of human being the human genome. Many techniques have been developed to enable accurate selection of the genes responsible for some of the desirable characteristics in some cases can be transferred from one organism to using these techniques in a quick and precise way.

The technical ability and skills of Scientists to play with and manipulate genes is called Genetic Engineering/ Biotechnology.

Even at this stage one can see the problems which can arise of some people can choose what to do with genes! The basis and consequences of the choices are not clear cut!

The Technical Ability to Genetically Modify Living Organisms even resurrect dead ones which Scientists have through biotechnology is frightening many people. In my view these powers acquired through Scientific knowledge, must be used in the context of ethical, moral and human rights perspective.

Already there are battles of Genetically Modified Organism, cloned plants, cloned animals and there are prospects of cloning human beings. In Uganda we have had cloned coffee and cloned bananas for sometime. In Israel chicken without feathers have been cloned.

Cloning has more than one meaning. When a pure cell line is selected and animals or plants are propagated from that pure cell lines clonal coffee, for example this is cloning.

When a female egg in harvested and its genetic information removed, then genetic information from a mature cell is transferred to the egg, the resultant organism is a clonal one.

When a fragment of DNA is duplicated and then through recombinant DNA is put back into the genome of an organism one has cloned DNA. Cloning has the idea of propagative genetic information in a “pure” form! However it is not always possible to exchange genetic information between organisms!

Agricultural Biotechnology
Uganda has two types of farmers, small scale farmers and large scale commercial farmers. However the majority of farmers are small scale farmers. In deciding on the application of molecular biology to farming, NARO has to decide which type of farmers to focus on.

Problem Definition
In order to direct molecular biology research and application to the needs of the Resource-Poor small scale farmers, one has to answer the following:

- What are the major problems of small scale farmers in Uganda?
- What are the potential contribution of biotechnology to agriculture?
- Under which conditions are molecular biology (biotechnology) solutions:

• Relevant in terms of expected output and absence of negative side effects.
• Achievable in terms of scientific and technical research and diffusible to and adoptable by farmers.
• Have comparative advantage in terms of appropriateness and feasibility, taking into account problem solving capacity of farmers and cost effectiveness.

In order to try and address these questions let us look at agricultural biotechnology.

Microbial Inoculation of Plants
Microbial inoculation technology is concerned with the selection and multiplication of plant beneficial microorganisms such as those for improved plant nutrition (biofertilisers) and for improved biological control of pests weeds and diseases (biological control agents).

Biofertilisers
Many soil microorganisms may enhance the nutrient uptake of plants. The natural processes of replenishing nitrogen used up by crops are too slow to sustain crop productivity. Some microorganisms such as the blue-green algae (cyanobacteria) the soil bacteria Azotobacter, Klebsiella, Bradyrhizobium, Rhizobium and an Actinomycetes are capable of fixing nitrogen from the atmosphere.

The effective biological nitrogen fixation can avoid the costly and polluting use of nitrogen fertilizers.

Mycorrhiza Associations
These can be described as symbioses between certain fungi particularly Vesicular-Arbuscular (VA) mycorrhizas and roots of vascular plants. The VA mycorrhizal fungus is unspecific and can infect a very wide range of host plants. These infections can greatly increase the rate of uptake of nutrients particularly phosphorous and nitrogen from deficient soils. However more research is needed on mycorrhiza associations.

Plant growth-promotion rhizobacteria
The beneficial effects of these organisms fall into two categories:

• Growth promotion and
• Plant disease suppression.
Growth promotion is shown in increased seedling emergence, vigorous seedling weight, root system development and yield.

Some of the plant growth promotion rhizobacterial are thought to control root pathogens which hinder the complex expression of the plant postential.

Biological control agents
Certain microorganisms are natural pesticides, fungicides, bactericides and herbicides. There are over 100 bacteria, fungi and viruses that infect insects. Bacillus thuringiensis an anaerobic spore former produces a proteinaceous crystal, toxic against many insect species including gypsy moths, cabbage looper and others. The toxin is very selective and biodegradable and causes death in many susceptible insects. In addition Bacillus papillae is used to control larval stages of Japanese Beetle. There are some viruses which control some caterpillars. Collectrotrichum gloeosporioides, a furgus is used as a herbicide in rice and soya bean.

In less intensive and low input agricultural systems biofertilisers and biological control agents are of great importance.

There is need for developing rapid assays for biological activity to select useful organisms which can improve plant performance.

Plant cell and Tissue culture
The basis of this technology rests on many plant species having the ability to regenerate a whop plant from a single cell. A single plant can be derived from a leaf, root, anther meristem or protoplast that can be grown in test tubes with appropriate culture medium. There are various techniques employed in this process such as embryo rescue, in-vitro selection/multiplication somaclonal variation etc.

These methods are relatively simple and straight forward which can be used for plant improvement or propagation of endangered species, and are very applicable in the Uganda situation.

As an off shoot of cell and tissue culture there is plant culture which is used widely as a method of producing quinine, morphine, nicotine and many other products. This is similar to the use of microorganisms to produce certain products.

Fermentation Technology
For thousands of years humankind has been taking advantage of activities of microorganisms to produce food stuff and drinks and to dispose of waste products. Fermentation is now used widely for food stuff and drinks and to dispose of waste products. It is the oldest application of using whole organisms to produce desirable products.

The fermentation process involves three phases namely:

• Acquisition and selection of organisms with desirable characteristics.
• Fermentors or bioreactors which may be simple or very complex depending on the desired product.
• Harvesting and product recovery.
The efficiency and yield of the process can be increased through the selection of more productive microbial strains and the control of production conditions.

Important fermentation products include alcoholic beverages ethanol, milk processing, production of amino acids, and antibiotics, single cell proteins and biogas production. All these are important for rural farmers and improved techniques can help improve nutritive value of some of the fermentation products.

Perhaps the most out-standing fermentation process is seen in ruminants which have the capacity to utilize cellulose, the most abundant biomass, as a source of energy and carbon. The use of cellulose as a source of glucose for humans is a very important area in need of research.

Recombination DNA
Technology

Recombinant DNA (rDNA) technology is the most dynamic area of the application of biotechnology to transforming living organisms. The techniques involve insertion of a piece of genetic material into the host cell genome, and may involve DNA probes, transformation of microorganisms or other organisms and rDAN vaccines.

The transformation of organisms (e.g bacteria) involve the following stages:

• Identification of a target gene and isolation of DNA;
• Characterization of DNA;
• Transfer of DNA to the host;
• Cloning; and
• Expression.
The transformation of host organisms can lead to increased production of metabolites and synthesis of new products for example the production of Bovine somatotrophin by bacterial cells Bacillus subtilis.

The other important area of recombinant DNA is the production of vaccines by DNA transfer into host organisms.

There are basically three types of DNA vaccines:
• Deletion mutant vaccine — genes coding for virulent properties are deleted and the resulting mutant will produce antibodies without pathogenicity;
• Subunit vaccine where a DNA subunit responsible for immunity is transferred to the host then the host will resist the invasion; and
• Carrier vaccine — genes coding for immunogentic antigens of pathogenic organisms are introduced into a vector of a known non pathogenic organisms. The vector will subsequently express the foreign genetic information coding for antigens.

However these techniques are very expensive and would be suitable only for commercial farmers or in real emerging epidemics.

Animal Production
Very many animals have been cloned as away of experimenting to produce the exact replicas of certain animals. But the techniques of cloning animals have inherent problems:

• The egg used is deprived of its own genetic information. So the egg does not contribute any genes to future organisms.
• The genes used are “old” in that they have undergone numerous repairs and may have undergone minor genetic mutations which may turn out to be important in the young offspring.

The animals which have been cloned so far show very early aging and some old age diseases seem to set in early. These animals have not lived long enough to indicate the long term effects of cloning.

For these reasons many governments have not sanctioned Human cloning.


© Martin Malungu


The dangers of human cloning
For the lay man, human cloning would involve a “production” of a viable child without the genetic intervention of a second parent! If the Scientist think that this is possible, then they cannot go on and deny “The Virgin Birth”. This type of cloning would actually proliferate Virgin Births.

The proposed human cloning, which cloning has been carried out in many domestic animals, involves getting female eggs, removing their genetic information from mature cells from any other part of the body or from mature cells of another person.

It is important to note that the egg is first deprived of its genetic information and then genetic information (DNA) from cells of a man or women are inserted into the egg(s). The offspring will have genes from either the man or the women but not both. If DNA is from a woman’s cell then all being well you will have a girl and DNA from a man’s cells will produce a boy.

If the DNA from cells of the owner of the egg leads to a child, you have a kind of Virgin Birth, that child will have no father. If on the other hand the egg gets DNA from a man’s cell, the boy will have “no genetic” mother, another type of the Virgin Birth.

The first complication of these children is that they both have “surrogate” mothers since they have no genetic inheritance from their mothers through the eggs. But worse still, No man has any genetic paternity claim on the girl and the mother has no genetical maternal claim on the boy.

Do children have rights of being genetically linked to their parents and to know that this is so?

The second major complication is the use of women as factories for empty “egg shells” where genetic information from some source could be inserted in order to produce cloned children, which children are genetically weakened.

In order forth women to produce these eggs they are subjected to all sorts of unnecessary medicaments and intrusive medical procedures in order to harvest the eggs. Many of the procedures do violate women’s rights.

These things would happen assuming that all goes well. Things go well only about 10% with 90% failures. The famous sheep cloned in Scotland, Dolly, was produced after more than 220 trials i.e. more than 220 eggs were wasted before success was arrived at. And at two Dolly was already aged.

When a cloned egg is reintroduced in the womb, many things may happen:
• It may fail to implant in the womb.
• It may implant and then stop growing.
• It may implant and then abort-spontaneously.
• It may implant and grow internal or external abnormalities such as headless, limbless, partially formed lungs, improperly formed alimentary canal. All these and many more have been found in cloned animals.

Science has a culture of publishing only its successes and keeping quiet at its failures!

In my view before cloning is extended to human being, we need much more information, knowledge and under-standing of the behaviour of newly formed DNA in sperms and ova, and the genetic behaviour of “old DNA” from mature already differentiated cells!

Will it not be a very sad world where “mothers” can make no claim to cloned boys, and “fathers” can make no claim to cloned girls?
Ethical issues and Biosafety
However there is need in all biotechnology experimentation and application of results to do the following:

• Risk Assessment — taking up all the Scientific and Social issues that pose potential risk and developing safety precautions to address them.
• Risk Evaluation — setting up specialized ethical review committees to offer advice to researchers on the ethics of their projects carrying out environmental, medical and social studies prior to selecting operational areas.
• Exchange Information with stakeholders and mass media including intrinsic issues of gene transfer between species and ecological impact of transgenic organisms.
• Sharing information and technology and data with all interested parties so as to bring about informed debate.
• Getting Consent from individuals and Communities to have trials or releases in their area.
• Continued study of long term effects.



In whatever area biotechnological research and applications there are delicate considerations between doing good and doing evil to living things particularly when things are done on the basis of choice of individuals whose interests are paramount. What are community interests? What are environmental consequences of short and long term of biotechnological applications? What are ethical principals for ethical biotechnology. Are all types of activities justified because they are labeled scientific? Does Scientific knowledge, technical and manipulative skills give someone a right to do whatever such a person chooses to do?