Original Article: Lewis, G.D. et al., Science Translational Medicine 2, 33 (2010).

Visits to biochemistry labs are frequent in our lives. Often we give blood to know levels of different metabolites, such as glucose or cholesterol. Instead of looking at a handful of metabolites, a group of scientists from Harvard Medical School has screened more than 200 metabolites before and after exercise. Interestingly, the levels of 21 of these metabolites changed significantly following exercise. The study also showed significant differences between physically more fit and less fit individuals after exercise. Following exercise, more fit people had greater increases in the biological markers of fat-burning and had decreased oxidative stress -a state where the balance between oxidants and antioxidants shift towards damaging oxidant side. Hence, fit people can get better results following exercise by efficiently removing waste materials. Moreover, exercise increased the levels of “niacinamide”, a compound which modulates insulin sensitivity. This increase was more prominent in leaner individuals and was maximized in fast marathon runners after exercise. It has been long known that obese and less-active individuals had greater tendencies to develop Type II diabetes where insulin action is impaired due to decreased sensitivity of the body to this molecule. Understanding the biochemistry behind the exercise may lead to identification of small molecules mediating its beneficial effects. These molecules may then be used to boost up metabolism or treat diseases. Until then, it is best to exercise and stay fit.

2- Our scents make us targets

Original Article: Carey, A.F. et al., Nature 464, 66 (2010).

Are you avoiding spending time outdoors in summer evenings because most of your time has to be spent chasing away the unwelcomed attention of mosquitoes? If so, then you must be one of those “lucky” people whose perspiration contains a key chemical that makes you irresistible to the six-legged bug. Scientists at Yale University have identified a key chemical compound that is detected by one of the mosquitoes’ 27 smell-receptors in their antenna. These smell-receptors are tuned to detect the key chemicals from hundreds of meters away which make people who secrete large amounts of these key chemicals in their sweat vulnerable to frequent mosquito attacks. Depending on the species, usually only the female mosquitoes bite humans, mainly on their feet or lower legs. More importantly, mosquitoes carry several deadly diseases such as Malaria and West-Nile dengue fever. In fact, Malaria is one of the deadliest and the most neglected diseases, affecting more than 500 million people and killing more than 3 million every year, mostly in sub-Saharan Africa. Sadly, the majority of deaths occur among children. Therefore, these types of studies, far from being trivial, may in fact lead to a better understanding of those mosquito-borne diseases, and hopefully may lead to the production of more effective drugs both for the prevention and the cure of diseases as well as better mosquito repellents and traps.

3- We are not alone in our body: Genomes of microbes living with us

Original Articles: Qin, J. et al., Nature 464, 59 (2010) & The Human Microbiome Jumpstart Reference Strains Consortium, Science 328, 994 (2010).

New advancements in DNA sequencing technology allow scientists to sequence genomes of microorganism living in their natural habitat. Human body contains roughly ten times as many microbes as human cells. As part of Human Microbiome Project, scientists are decoding the DNA sequences of all microbes living in several parts of our body such as skin, mouth, gut, respiratory tract and urogenital tract. Two independent teams from US and Europe have produced the first results of DNA sequences of microbes living with us. The projects have initially focused on bacterial genomes but intent to sequence viral and fungal genomes as well. The US team has generated a set of 178 bacterial reference genomes and is aiming to generate many more. In the second project funded by European Union, scientists sequenced the entire microbial DNA in the gut instead of sequencing them individually. They have sequenced more than 3 million bacterial genes, nearly 150 times more than our own (humans have only ~20 thousand genes). Importantly they have found that bacterial species are different in healthy individuals compared to the individuals with inflammatory bowel disease. Throughout these projects, scientists are trying to reveal significant information about the role of different microbial species in health and disease states.

4- Seeing with the sound

Original Article: Yovel Y et al., Science 327, 701 (2010).

Bats, dolphins, shrews and swiftlets use sound waves for navigation and hunting. They emit short sonar pulses and listen to the echoes reflecting back from solid objects. Microsecond differences in the arrival times of echoes are coded by detector neurons and used as a main cue for positioning objects in an environment. This phenomenon is known as biosonar. A recent study published in Science reveals one unknown part of this perfect sound processing strategy. The study shows that bats do not center the sonar beam on the target. Instead, they aim to match the maximum slope of the beam to the target in order to increase the signal-to- noise ratio. Around the sharp edge, small variations of the target position can be detected as a clear signal change in reflected sound intensity. Furthermore, the researchers showed that if the environment is very noisy, bats could bias this critical point to increase amplitude of the echoes. As it turns, this powerful technique has already been employed by humans in engineering and used in various technological tools such as atomic force microcopy. Whether this strategy is used in general by other echolocating animals remains to be answered.

In the industrialised countries biotechnology has been one of the fastest developing and most promising fields of research in recent decades. It is defined as the application of biological organisms, systems or processes to manufacturing and service industries. There are sub-divisions within biotechnology — such as fermenter technology, genetic engineering, enzyme technology, environmental technology, animal and plant biotechnology. In this article, we will look briefly at some topics in plant biotechnology which deals with the building- blocks of agriculture, horticulture, and the food, chemical and pharmacological industries. Already, commercially important applications of plant biotechnology such as transgenic vegetables and fruits, insecticide-resistant corn and cotton, herbicide-resistant beans and synthetic seeds have begun to appear in the market-places of America, Japan and Europe. This trend is set to expand dramatically in the coming decade.

Molecular biology

Molecular biology tools figure importantly in plant biotechnology. Plant breeders are trying to discover and determine the best combination of the genetic characters in different plants with the help of Randomly Amplified Polymorphic DNA (RAPD) and Restriction Fragment Length Polymorphisim (RFLP) techniques. The aim is to identify desirable characters and their precise location on chromosomes. Then, recombinant DNA technology can be applied to transfer a particular gene into a plant cell so as to alter and improve its original character. This technique enables us to, for example, produce flowers of a specified shape and colour or plants which secrete anti-fungal and anti- insect proteins.

The Human Genome Prced(HGP) is one of the grandest scientific projects of the end of the 20th century. The location, functions and base sequences of all human genes will be identified and the information used for diagnostic purposes such as controlling cancer or ageing genes. There is another, comparable project on model plant Aribidopsis which contains the smallest genome size in. The gene sequences of Aribidopsis are expected to have been fully mapped in ten years time. Japanese scientists are trying to determine the gene sequences of rice by using the mRNAs. Plant genome projects will be as important as the HGP in the coming century, because understanding the gene structures of plants may, by permitting us to produce ‘new’ genetically enhanced foods, provide the solution to the problem of ensuring food supplies while protecting the environment.

Plants genetically resistant to insects and herbicides

Insect pests and diseases caused by fungal, viral and bacterial pathogens are responsible for substantial losses in crop yields world-wide. The chemical control of insects and fungal pathogens represents a large segment of the crop- protecting business, currently estimated at US$ 8.7 billion annually. The global losses due to insects or diseases, despite extensive use of pesticides, are still 12-13%. Although all plants have some defensive systems to protect against insects and pathogens, the crop varieties used in modern agriculture often lack sufficient resistance. A kind of ‘killer proteins’ secreted by plants and micro-organisms prevent the larval development of insects or fungal and bacterial growths. The ‘killer protein’ genes are transposed to make genetically resistant varieties of such crops as corn, cotton, tomato, yellow squash, tobacco, and other model transgenic plants. For example, transgenic potato plants expressing a synthetic gene from B.thuringiensis sub sp terebrionus at high level exhibited strong resistance to Colorado potato beetle (CPB) in a large number of field trials and have recently been approved for commercial release. Potato growers currently spend US$ 75-100 million annually on the protection of about 480,000 hectares of potato. The CPB resistance potatoes will significantly reduce their use of environmentally undesirable insecticides.

Another example: Roundup is a commonly used herbicide which deactivates one of the chloroplast enzymes and so causes the death of the target plant but which also negatively affects crops. Plant molecular biologists identified a highly expressing enzyme which can defuse the effect of Roundup. This strain has been successfully transferred to some important crop species such as a rice which is now genetically resistant to the Roundup herbicide.

Natural plant metabolites in cell suspension cultures

Plants sometimes produce secondary metabolites (unlike primary metabolites such as DNA and amino acids) to adapt to their environment or to protect themselves from enemies. There are more then 100,000 types of secondary metabolites secreted by many kinds of plants which count as ‘natural products’ used particularly in the dyeing, pharmacology and cosmetic industry, and in insecticide and herbicide production. Some of the secondary metabolites are produced in batch cultures (growing plant cells in suspension medium) in plant biotechnology laboratories. Not all metabolites are in production, only a few and (for the present) economically non-viable metabolites have been produced over the last few decades. However, some metabolites are extremely important such as vincristine and taxol natural products which are used as anticancer drugs in medicine. Taxol is naturally produced by taxus tree (Taxus brevifolia), and costs approximately US$ 1.6 million kg-i. Taxol can be synthesized in chemistry labs in 52 steps, but is so laborious and expensive as not to hold much hope for commercial application. Vincristine is the rarest alkaloid found (1 part in 5 million dry weight) which is naturally produced by Madagascar Periwinkle (Catharanthus roseus) and it costs US$ 3 million kg-i. Five to six year- old trees are used to extract these ‘fine chemicals’. 250 kg of taxol is needed throughout the world each year. That means we must destroy one million taxol trees every year in order to supply this amount. This is not a cost-efficient or environment friendly process. Today, some economically less important chemicals are produced in bioreactors but, as yet, valuable Chemicals like taxol and vincristine are still waiting for the development of economically viable in vitro production techniques. If that aim is achieved, destroying trees for extraction will stop, production will be increased and prices come down.

‘Edible vaccine production in transgenic plants

Plant and animal protein structures are almost similar. Today, micro-organisms are used to produce vaccines. However, plants can easily be made to produce some pharmacalogically important antigens, and can economically be used as an alternative method. For instance, the production of hepatic B surface antigen (HBsAg) was expressed by transgenic tobacco plant. Although the expression level was low, HBsAg was expressed with similar physical properties to the serum-derived protein. The antigen extracted from tobacco has recently been demonstrated successfully in mice.

There are some other reports on vaccine production against cholera and malaria by transgenic plants. The demonstration that vaccine antigens can provide new opportunities for bio-farming of vaccines, If the antigens were orally active, food-based ‘edible vaccines’ could allow economical production and delivery in developing countries. Astonishingly, the vaccines containing edible plants may be developed and will be commercially available, and in the very near future, children in developing countries will be eating tailor-made polysaccharide containing potato as a nutrient, as well as a vaccine to protect them from cholera. The ‘edible vaccine’ plant foods will be one of the most amazing new products of the next century.

Micro-propagation and somatic embryogenesis

Plant cells unlike animals, have the potential, known as totipotency, to make individual plant organisms. Plants can be regenerated in biotechnology labs by the help of tissue culture techniques. Natural seeds are generally heterogeneous and lose desired characters in their phenotypes. Therefore, seed manufacturers produce homozygous (wild type) products but this is time-consuming and uneconomical. Plant biotechnologists are dealing with this problem by regenerating the plant in vitro. Micro-propagation and somatic embryogenesis are two principal ways of plant regeneration in vitro.

Micro-propagation involves the germination of seeds, cutting axillary buds of regenerants and then distributing on solid media to get new regenerated plants. Thousands of similar genomic structure regenerants can be produced by this technique. Although this technique needs less labour and money on a small scale, there are some technical problems in scaling up.

There is an alternative but less known somatic embryogenesis technique. It offers the production of ‘synthetic seeds’ in vitro on a large scales. A few model plant synthetic seeds such as carrot, alfalfa, spruce and celery have been successfully achieved in bio-industries. This technique involves the production of large numbers of synthetic seeds and then their encapsulation by variety gels. Subsequently, the synthetic seeds grow successfully in greenhouses. The aim in this field is to achieve large scale production of economically important plant seeds containing desirable characters.

Ethics

The question of what the effects will be of transgenic products on human health and on nature still remains unanswered. Should we answer this question now or should we wait until we see the bad consequences? It is our view that this question should be answered by scientists, philosophers and lay people before the products are released onto the market.

It is my belief that the earth has enough resources to provide the well-being of its human population, and human beings can enhance these resources by sensitive application of the new technologies, some aspects of which we have just looked at. However, some of the major problems of food supply and environmental degradation arise not from the lack of resources but from inequalities in access to and distribution of those resources, not least of which is the resource of knowledge and technology. If we are to use the new technologies for the benefit of human beings generally, without destroying the environment we all share, the political and social problems of distribution and transfer of technologies must be addressed. We need to live co-operatively and collaboratively both with ourselves and with our planet.

References 

• Mason H. S. & Amtzen C. J. (1994)‘Transgenic Plants as Vaccine Production System’, Trends In Biotechnology (Elsveir Trends Journals). 13(9), pp.388-392.
• Onishi N., Sakamato Y. & Hirosawa T.(1994) ‘Synthetic Seeds as an Application of Mass Production of Somatic Embryos, Plant Cell, Tissue and Organ Culture (Kluwer Academic Publications), 39, pp.137-48.
• Pezzuta J., (1996) ‘Taxol Production in Plant Cell Culture Comes of age’. Nature Biotechnology, 14, p.1063.
• Shah M.D.. Rommens C.M T. & Beachy R.N. (1994) ‘Resistance to Diseases and Insects in Transgenic Plants: Progress and Applications to Agriculture’, Trends In Biotechnology (Elsveir Trends Journals), 13(9), pp.362-7.
• Smith J.E. (1981) Biotechnology, Edward Arnold Ltd, London, pp.1-6.
• Stogkigt J., Obitz P., Falkenhagen H.,Lutterbach R. & Endress S. (1995) ‘Natural Products And Enzymes From Plant Cell Cultures’, Plant Cell, Tissue and Organ Culture (Kluwer Academic Publications), 43. pp.97- 105.