“I think the biggest innovations of the 21st century will be at the intersection of biology and technology. A new era is beginning.” — Steve Jobs
While analyzing the effects of radio frequency heating on hypothermia in the year 1941, Canadian electrical engineer John Hopps read that if the heart stops beating due to an acute drop in temperature, it could successfully be brought back to life artificially using mechanical or electrical stimulation. This research was carried forward to develop the first ever cardiac defibrillation machine which was primarily then used by Hopps to regulate and consequently revive a dog’s heart. By the mid-80s, artificial cardiac pacemaker installation became a recognized routine procedure saving thousands of lives all over the world. Serendipity through inspired insights has often been regarded as the key to scientific breakthroughs, additory advances and an inquisitive mind looks beyond the anomaly considering the results worthy of a follow up. Creating novel opportunities for researches around the globe, advanced technologies being introduced time and again have disparate and diverse applications from the originally intended conventional configurations combining the scientific laws of nature.
The discovery of the Green Florescent Protein (GFP) led to the concept of genes being used as expression reporters modified in the form of biosensors when introduced in organisms via transgenic channels. Considering its widespread potential to satisfy the emerging needs of researchers, different mutants of GFP were engineered. The first major developmental refinement was a single point mutation (S65T) that was reported by Roger Tsein in Nature, 1995. This mutation was known to remarkably advance the spectral characteristics of GFP and its photostability causing a shift of the excitation peak to 488 nm, peak emission at 509 nm. In 2000, a genetic ‘circuit’ was created in Escherichia coli that caused the cells to blink light in a lighthouse. The underlying idea stated to transform microorganisms to behave like microchips of tiny programable computers. The circuit, “Repressilator” comprised of three repressor genes, one of which turned on the gene for GFP which upon activation emits green light. Consequently, researchers crafted a ‘toggle switch’ to oscillate the circuit and alter its pattern based on the culture growth conditions.
Mendelian genetics observes the fact that trillions of cells of an organism have the genotype which is just as same as that of the single celled zygote. The cloning of Dolly, a Finn-Dorset ewe reaffirms the carriage of genes and genotypic consistency. Molecular biology and genetics of bacteria and phages aided the acceptance of cell interactions as an essential share of normal embryogenesis. Based on neoteric findings, it has now been realized that most of the embryonic cells of arthropods and nematodes make developmental decisions based on the chemical signals that they receive from other cells; much like vertebrates. The repetition of the signaling and responding cycles can be said to rely on the ‘Genotype-Environment interactions’: the local setting of a cell being influenced by the neighboring cells. The genotype of a cell and its previous decisions on its proliferation determine its options for responses to the signals currently being received. (Wolpert, 1969)
By the early 1970s, scientists had revealed that they could engineer successfully synthetic genes, the de novo generation of nucleotide sequences of interest. With the development of the Polymerase Chain Reaction (PCR) in the 1980s, the study of gene expression, structure and function has exceptionally and accurately enabled us to synthesize short oligonucleotide sequences, substantially enabling a myriad of overtures, certainly not the least of which has been the Human Genome Project. This eventually threw light upon the de novo synthesis of increasingly larger constructs of DNA. Synthesis followed by ligation of these large constructs of DNA fragments of a template preceded the enzymatic transcription of RNA leading to the anew creation of the poliovirus genome in 2002 from which the virulent virus was suitably recovered post transfection into permissive cells. Constructive technologies in DNA synthesis have generated enthusiastic responses regarding the assembly of genetic circuitry allowing efficient and rapid synthesis of other viral or pathogenic genomes for therapeutic research and development. Moreover, several studies have demonstrated in recent times DNA amplification being made available and affordable improving its error rate to help generate reliable results.
Combinatorial chemistry generating technologies and processing of libraries used for the rapid creation of large number of synthetic compounds are now been used typically for purposes of screening for hustle against biological drug targets. Solution-phase parallel synthesis has now been the preferred technique of choice in pharmaceutical companies directed primarily by the proceedings in laboratory automation, instrumentation and informatics. Often a common multicomponent reaction termed as the ‘UGI Reaction’ involving an isocyanide, an aldehyde, an amino acid and a carboxylic acid has been used to identify the desired biological effects representing a 400-fold increment in discovery efficiency as compared to conventional methods. Using high-throughput screening methods pharmaceutical industries synthesize and screen millions of potential ligands each year. Professionally, information derived from screening technologies is often held in proprietary databases. However, a new public database recently proposed as a part of the National Institute of Health Roadmap raises concern of being particularly worrisome in regard of optimizing lead compounds that could be capable of targeting specific cellular proteins.
Synthetic Biology, as biologists may see, is a fledging five-year-old progressive field dedicated to unearth the underlying principles of cellular functions. Analyzing the basic modules of synthetic gene circuits, which, like Legos™, can be spliced together, synthetic biologists develop efficient biochemical logic boards capable of controlling both intra as well as extra cellular activities. Prototypes of ‘DNA Computers’ capable of rationally examining mRNA disease indicators in vitro have been designed; the technology requires nanoparticles to be injected each of which operates as a tiny computer individually interrogating cells and arresting the presence of diagnostic DNA markers like overexpressed mRNA. Synthetically designed bacteria can detect chemical and biological agent signatures, could possible promote sustainable environment conservation and diagnose or fix faulty genes.
Succeeding the genome sequencing of the H1N1 Influenza A virus, several questions were raised criticizing the decision to have the studies published in virtue of the 1918 virus being a potential threat, an agent of bioterrorism. As summarized by an article published in 2003 with respect to pathogenic strains of the H5N1 virus being malevolently used, virologist Robert. M. Krug of the University of Texas stated:
“There is every reason to believe that the same recombinant DNA technology can be used to render this H5N1 virus transmissible throughout the human population. Furthermore, it should be possible to introduce mutations into such a recombinant virus rendering it resistant against currently available influenza virus antivirals possessing an HA antigenic site.”
Responsibly understanding and harnessing genomic variation could contribute significantly in improving the state of traditional biological sciences at present. Genomic medicine, biomedical research communities, the future trajectory; possibly the convergence of nanotechnology and molecular biology promise multiple new approaches to molecular diagnostics and drug delivery. Biomedical advances in aerosol delivery techniques have also been able to improve patient adherence. Gene therapy technologies are still restricted to research on rodents and primates although, substantially impressive progress has definitely been made and clinical success seems to be on the horizon. Having mentioned all of it, some futurists have befittingly believed that the convergence of Bio-, Nano-, and Information Technologies along with neuro and cognitive sciences could possibly bring about a transformation as powerful as the Industrial Revolution.
About the authors:
Ms. Ananya Mukherjee is currently pursuing her graduation in BSc. (H) Botany from Deshbandhu College, Delhi University. She has won international prizes at debating competitions and has great flair for genetics and evolutionary studies. She had the opportunity to work with JUSCO Tata Steel Environment and Sustainability Department, and wishes to be a scientist in future, helping the mankind on a greater scale.
Mr. Arpit Das is currently enrolled as a student of BSc. (H) Botany in Deshbandhu College, Delhi University. He has won fellowships from JNCASR and Indian Academy of Sciences to be a part of research in the field of developmental and stress biology. Apart from an enthusiast of natural sciences, he volunteers in environmental NGOs like WWF and Greenpeace.