BIOINFORMATICS, BIO – MEDICINE, AND GENE MANIPULATIONS IN DRUG DEVELOPMENT AND FUTURE MEDICAL CARE.

Dr.T.V.Rao, MD

Bioinformatics is an emerging science which brings together the fields of Microbiology, Molecular Biology, Bio Technology and Genetics under the fold of computers and Software Advances in Computer Technology. Thanks to James Watson – Crick in basic understanding of the Bacterial DNA (genome). The coding of Chromosomes through the Super Computers; Databases and Software Technology perfecting the code of life, now Bioinformatics has become a big enterprise. Research reports, from all round the world (300 Laboratories) presented recently during a major genome conference at Cold spring harbor laboratory showed clearly that an exciting technology is born. We doctors in the past looking the problems of life and disease through clinical medicine, few laboratory tests and other technical advances. The Bioinformatics is changing the entire concept, in future we may be compelled to view life and disease through the Chemistry of Genes. The facts about the human genome project were made public on the Internet by US department of energy and National Institute of Health, making the approach easier to any scientist or Doctor to learn the genomic science to utmost detail.

1. Basic findings of Genome Project: a) Basis of life is equal between two individuals upto 99.9% extent, secret of difference lies in only 0.1%, contributing to our individuality. b) There are approximately 30,000 Genes. c) Genetic Mutations are common in males, so men are agents of change. d) so Genetic diseases are common in men.

2. Computer Speaks (Bio information): With feeding of complicated information to a computer, it speaks that life is a pack of information with a clear message that book of the life written in the complex DNA consisting of four letters. A.T.G.C.

A = Adenine; T =Thymine; G = Guanine; C = Cytosine.

At present we have > 85% of information on 23 pairs of Human Chromosomes. In future science expects that Physician can solve many mysteries of disease just looking into a computer and the greatest advantage lies in detection of most of the Genetic disorders. In future many diagnostic tests may be done by Bioinformed computers, the chip locating abnormal base pairs at different gene locations. Now in many Nations scientific organizations of repute are on a path to Bioinformatics with aim to make the recent science available to many.

3. Bioinformatics and Gene Therapy: Gene therapy suffered with many problems in the past will have a greater revival with better understanding of human genome. Many gene therapy trails will become virtual realities.

4. Bioinformatics and Proteomics: The knowledge of information about the Genes and Science of Genomics lead to science of proteomics To catalogue and analyse every protein in human system. The science of proteomics (Structural Genomics) will revolutionise the understanding of Hormones, Immunoglobulins targeting infections and Enzymes that build or break down energy reserves. We are aware now, that there are too, many proteins which guide our life (50,000 to about 2 millions). But few Proteins play the real orchestra, modifying different actions. Already many Bio Technology firms have started proteomics programme, if the events succeed to desired expectations there will be better quality of life serving to minute details.

5. Human Genome Project – Drugs of Future: At present we use certain drugs with a broad understanding to target only 500 proteins in the body, out of the 30,000 proteins already known to us. Because of the better understanding of Genome, Scientists have a good understanding on what happens if drug acting down to molecular level. Till now many drugs are experimented on trial and error basis mainly intervening at the level of signs and symptoms, and few at cellular levels.

With advances in Genomic Medicine there will be more rational approach in drug discovery and clinical application. In future it is possible to target the diseases like Diabetes and Cancer before the onset of physical disease (phenotypic expression). The scientific visions include interfering with the sick cell, sparing the healthy cells, making the therapy least toxic and harmful. The discovery in this direction lead to discovery of Monoclonal antibodies, choosing the particular receptor on the cancer cell responsible for propagation of disease. Already 12 such drugs are available in developed countries prominent being Herceptin, if blocks the HE-2/neu receptor, which is prominent on some breast cancer cells. Tepper’s group is on the way to find a Monoclonal which can block the common receptor for cancers like breast, prostate, lung and colon to create a super drug for many cancers. With better understanding on Bioinformatics Anti Cancer Drug discoveries will be target oriented with least toxic effects.

6. Genomic Based Drug Discovery: Alfred Gilman, a pharmacologist and winner of 1994 noble prize for his work on Cellular Signaling Mechanism, is now working with goal to trace the map of chemical pathways in the cells and use the knowledge to create virtual cell with all the pathways in a computer. Now the drug companies are using the Bioinformatics algorithms to predict the functions of proteins encoded by newly discovered genes. Many drugs discovers are moving to fast growing new area of Computer Science to fuel their endless quest for newer drugs and better targets.

7. Major Diseases on the List of Pharmaceutical Industry

The following diseases are being targeted by many drug firms with Bioinformatics include: AIDS, Mental Illnesses, Auto Immune Disease, Obesity, Alzheimer ’s disease, Heart Disease and Parkinson’s Disease.

From Experiments to Reality

The sequence of events from Discovery of Noble Laureate Joshua Lederberg (1958) on exchange of DNA within such chromosome pairs leads to process of homology recombination expressing in Genetic variation in the population. The present events of discovery by Mario Capecchi and Oliver Smithies applied the homology recombination in mammalian cell. The homologues recombination could take place between introduced DNA the cell Chromosome may even repair with the help of induced genes and awarded the Nobel Prize in 2007. The present study by them has targeted role of Genes involved in Mammalian organ development. Several human inborn errors an be targeted in events of malformation. If the future experiments are successful mouse models will be used for gene targeting The art of Medicine will be enriched with biology as source of future developments in Medicine.

Changing Role of Biology on Medicine: We are understanding more of Genes and inheretence.The quest to discover disease linked genes reaches all time high. Now it is understood the 3 million DNA bases in the Human genome have identified that about only one tenth, of one percent (Million) differ from one person to another. Variation in these particular letters called SNIPS or SNP’s, for single nucleotide polymorphisms have replaced genes as unit of heredity.

Role of Bioinformatics and Bio-Medicine on the Medical Profession: In the near future, every standard text book on Medicine, articles, journals published from reputed medical institutions emphasize the origin of disease on Genetic basis locating, few base pairs of Genes responsible for any complicated disease. The treatment approaches will be on targets of pathological process rather than vague remedies. We teachers in medicine should concentrate in understanding the role of Genes in disease and spread the message to our students. Let us learn to understand many diseases have a genetic basis and unlock the problem with a right key. Let there be more workshops, CME’s & Seminars on orientation of Bioinformatics and Biomedicine to our Doctors, so that we do not remain as Apes in front of a Bioinformed Computer.