Impact of Advanced Technology in Biology

“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.