Dairy Biotechnology

Module 1. Introduction to biotechnology

Lesson 3
FUTURE APPLICATIONS OF BIOTECHNOLOGY

3.1 Introduction

The present generation biotechnology has found immense applications as genetic engineering, recombinant DNA technology, protein engineering, animal cloning, stem cell technology as well as cell and tissue culture. The main target of biotechnology is to modify any available organism for the benefit of human beings by exploring genetic manipulation and engineering processes. Biotechnology is a vast subject, which has potential applications in almost all areas related to our basic interactions in daily life, including food, agriculture, medical field, environmental science, personal care and much more. Realizing the extensive scope and future prospects of the subject, developed nations started large-scale investment in biotech sector, encouraging clusters of small and large biotech companies, financing extended research activities and inculcating both the basic ideas and advanced levels of knowledge to youngsters in high schools and universities. The aim of these well-established economies was to lead the world in the latest technology, claim the research findings and rule the world market by being the first to supply biotech products. Whereas, the developing countries followed the trend, dreaming to uplift their national economy using biotechnology to increase job opportunities and attract global investors, thereby, yearning to gradually transform themselves into a developed nation. Biotechnology finds a large scope of application in medicine, agriculture, food, industry, environment and a host of other areas including development of species bioinformatics. Although, modern biotechnology has been extensively explored for providing solution to almost all the problems confronting human life, the major fields where biotechnology is actively used include completion of human whole genome sequence of different origin across the world, medicine (drugs, vaccines and diagnostics), Pharmacogenomics, Pharmaceutical products, gene testing, gene therapy, agriculture and cloning. Biotechnology is one of the fastest growing sectors across the world including India and elsewhere. This emerging field is going to take a leap forward in the next few decades ahead. Some of the most recent and advanced areas where biotechnology can find future applications with direct impact on human life are elaborated below.

3.1.1 Human genome project

The Human Genome Project has been an initiative of the U.S. Department of Energy (DOE) that aims to generate a high-quality reference sequence for the entire human genome and identify all the human genes. The DOE and its predecessor agencies were assigned by the U.S. Congress to develop new energy resources and technologies and to pursue a deeper understanding of potential health and environmental risks posed by their production and use. In 1986, the DOE announced its Human Genome Initiative. Shortly thereafter, the DOE and National Institutes of Health developed a plan for a joint Human Genome Project (“HGP”), which officially began in 1990. The HGP was originally planned to last 15 years. However, rapid technological advances and worldwide participation accelerated the completion date to 2003 (making it a 13 year project). There are approximately 30,000 genes in human beings. The whole human genome sequence available on the net as public domain will be the main focus of more intensive future studies for identification of specific genes and their linkage with common human diseases which will eventually be explored in their diagnostics, treatment and cure.

3.1.2 Drugs, vaccines and diagnostics

Drugs, vaccines and the diagnostics are the key elements in human health care where, biotechnology has played a vital role in the disease control and management. In this context, synthetic human insulin turned out to be the first biotechnology product approved for human health care at commercial level in 1982. Since then, more than as many as 170 biotechnology related drugs and vaccines have been approved by FDA, of which 113 are currently on the market. In addition, another 350 biotechnology medicines, together targeting over 200 diseases, are in the final stages of development. Some examples of the biotech products already approved during 2000s include medicines to treat pneumococcal diseases in children, diabetes, cancer and haemophilia. Further advancements in rDNA technology is likely to revolutionize new initiatives on vaccine development in the future. In this context, DNA vaccines have recently started the testing process and very soon are expected to eventually replace other methods of vaccine production. Conventional vaccines are made from either live, weakened pathogens (disease causing agents) or killed pathogens. Although, vaccines produced using live pathogens confer greater and longer lasting immunity than those using killed pathogens, they may carry some risk of causing the full-blown disease to develop. However, the current focus is on exploring individual proteins as antigens in sub-unit vaccines by recombinant DNA technology. DNA vaccines contain only those genes of the pathogen which produce the antigen, and not those used by the pathogen to reproduce itself in host cells. Therefore, DNA vaccines are expected to combine the effectiveness of live vaccines with the comparative safety of those based on killed pathogens. Several preventive and therapeutic vaccines for HIV are currently in early trials. DNA vaccines are likely to be more extensively available to developing countries than conventionally produced vaccines. Application of DNA vaccines could be more relevant to the third world counties since, such vaccines can be cheaper in comparison to attenuated and live vaccines. Moreover, DNA vaccines are more stable at normal temperatures. Refrigeration costs can significantly increase overall budget by 80 per cent in the vaccination program run in the tropical countries using conventional vaccines. However, there are still some uncertainties about the potential for vaccine DNA to “invade” the host’s genome and possibly trigger genes relating to tumor development. Therefore, a great deal of caution needs to be exercised while developing new DNA vaccines ahead.

Disease diagnostics is another area where modern biotechnology can play a significant role by rapidly detecting the presence of potential pathogens-implicated in various diseases not only in processed foods but also in clinical and environmental samples from the hospitals. The two key areas of biotechnology currently being explored in disease diagnosis include immunological assays and molecular techniques based on PCR and RT-qPCR. Monoclonal antibody diagnostic tests have been extensively used for several years and are now one of the most profitable areas of commercial biotechnology. These diagnostic tests are actually quite inexpensive to produce, and present enormous opportunities for some developing countries to enter the international biotechnology market. The second area of biotechnology used for diagnostics is DNA technology. DNA probes, which use isolated segments of DNA to “attract” complementary gene sequences from pathogens, are already on the market. However, the major focus is now on exploring PCR techniques including RT-qPCR that have completely revolutionized the concept of diagnostics as these are extremely fast methods apart from being highly sensitive and specific. Moreover, they are relatively cheaper to produce, and are usually more stable in transit and in tropical climates than conventional diagnostics. Further advancements in new generation of biotechnology have led to the emergence of more sophisticated high throughput techniques like DNA chips and microarrays which have opened new avenues in DNA diagnostics and bright prospects in disease diagnosis and detection of high risk food-pathogens in foods. Microarrays allow the detection and analysis of thousands of genes in a single small sample, giving the power of many DNA probes in one small array. Microarray technology is also expected to greatly increase the efficiency of drug discovery, although no drugs have as yet been developed using the technology.

3.1.3 Drug discovery and development

After the completion of the human genome project, pharma industry is now exploring the vast amount of knowledge generated from therein in the discovery and development of novel drugs. By judiciously using genomics approach, it is now possible to make drug therapy more precise and effective. Advancements in genomic technology have provided the necessary impetus to pharma industry to use this strategy in which engineered proteins specifically target diseases for better compliance and safety in the affected population, enhanced delivery and maximum efficacy. It is going to provide the platform for exponential growth and development of drugs and vaccines for the benefit of mass human population. With the unraveling of the human genome and the use of modern biotechnological tools to screen and produce active molecules have grown enormously resulting into the discovery of thousands of new molecules to be developed and tested in disease management.

3.1.4 Stem cells

Generally speaking, stem cells are self-renewing primitive cells that can develop into functional, differentiated cells. They have the unique ability to be manipulated by genetic engineering to give rise to specific cell types. With regard to human longevity, the focus is currently on exploring human pluripotent stem cells (hPSCs), which are unique because they can develop into all cells and tissues in the body. The pluripotency of human stem cells creates the vast potential for humans to grow cells, tissues, and even organs in a controlled laboratory setting, for use in applications from acute emergency care to treatment of chronic, debilitating diseases. Stem cells and their applications will be elaborated in a separate chapter.

3.1.5 Animal cloning

This technology has the potential to produce genetically matched cells for use in repairing organs damaged by degenerative disease. The process of making genetically identical copies became science-fact when in early 1997, Dr. Ian Wilmut and his colleagues at the Roslin Institute unveiled Dolly- the first cloned sheep. Dolly demonstrated that the nucleus of an adult cell could be successfully transferred to an enucleated egg to create cloned offspring. The birth of Dolly was a significant achievement because it demonstrated the ability of egg cytoplasm to “reprogram” an adult nucleus. Reprogramming enables the differentiated cell nucleus to express all the genes required for full embryonic development of the adult animal Following Dolly’s creation, cloning has been used to replicate mice, goats, and cattle from donor cells obtained from adult mice, goats, and cattle, respectively. These examples of cloning normal animals from fully differentiated adult cells demonstrate the universality of nuclear reprogramming. Using nuclear transfer, multiple identical copies of animals can be produced that express only the genetic traits of the animal whose cells were used as the nuclear donors. While the frequency of success is currently low, it is expected to improve, as the fundamental mechanisms of nuclear reprogramming by egg cell cytoplasm become better understood. The scope and potential applications of animal cloning have been listed below

• Rapid multiplication of desired live stocks and their germ plasm.

• Conservation of the rare endangered animal species.

• Use of cloned animals as research models to study genetic(cystic fibrosis) and other diseases related to aging and cancer, drug discovery and evaluation of gene and cell therapy (human medicine).

• Transgenic applications- production of transgenic live stocks for expression of value added human pharmaceutical proteins.

• Production of animal organs for xeno-transplantation in affected human population.

• Improvement in the quality and quantity of foods and fiber products reducing environmental pollution and improving animal disease resistance.

3.1.6 Nanobiotechnology

Employing nanodevices - high-tech, miniaturized devices on the scale of billionths of a meter, nanomedicine manipulates human biology at its most basic levels. These tiny tools enable scientists to play on the size scale of biomolecules itself, just as a mechanic works on a car’s engine using tools that are on the same scale as the engine. Nanotechniques may be our best armament in treating and even curing-stubborn diseases such as cancer and diabetes. Researchers have now designed clever ways to power nanomachines with biologically based components. Nanomoters, as well as nanotweezers - the mechanical and energy aspects of which are completely built from DNA are revolutionary innovations that will enable scientists to unleash microscopic robots within the human body on missions to correct the ravages of age.

3.1.7 Artificial organs

The medical makeover is just a few years away. We are talking about checking in to a clinic near you and checking out with new body parts. Advanced prototypes of nearly every single body part already exists in research laboratories. Not farfetched, tomorrow’s body part shop is an extension of work that began in the mid-twentieth century. Dr. Willen Kolff, inventor of the kidney dialysis machine, emigrated to the United States from the Netherlands in the mid-1950’s and became known as the “father of artificial organs” after he developed the artificial heart at the Cleveland Clinic, and created the nation’s first artificial organ research program at the University of Utah in the 1960’s. Research teams from around the world are working on projects to produce mechanical body parts that would vanquish many diseases and disabilities with which thousands of people struggle. Replacement parts for worn out or damaged human organs, along with applications of genetic engineering and stem cell research, hold great promise both today and in the not-so-distant future for extending the healthy human life span.

3.1.8 Pharmacogenomics

Pharmacogenomics is the study of how the genetic inheritance of an individual affects his/her body’s response to drugs. It is a coined word derived from the words “pharmacology” and “genomics”. It is hence the study of the relationship between pharmaceuticals and genetics. The vision of pharmacogenomics is to be able to design and produce drugs that are adapted to each person’s genetic makeup.

Pharmacogenomics results in the following benefits.

1. Development of tailor - made medicines.
Using pharmacogenomics, pharmaceutical companies can create drugs based on the proteins, enzymes and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize therapeutic effects but also to decrease damage to nearby healthy cells.

2. More accurate methods of determining appropriate drug dosages.
Knowing a patient’s genetics will enable doctors to determine how well his/ her body can process and metabolize a medicine. This will maximize the value of the medicine and decrease the likelihood of overdose.

3. Improvements in the drug discovery and approval process.
The discovery of potential therapies will be made easier using genome targets. Genes have been associated with numerous diseases and disorders. With modern biotechnology, these genes can be used as targets for the development of effective new therapies, which could significantly shorten the drug discovery process.

3.1.9 Gene therapy

Gene therapy may be used for treating, or even curing, genetic and acquired diseases like cancer and AIDS by using normal genes to supplement or replace defective genes or to bolster a normal function such as immunity. It can be used to target somatic (i.e., body) or gametes (i.e., egg and sperm) cells. In somatic gene therapy, the genome of the recipient is changed, but this change is not passed along to the next generation. In contrast, in germline gene therapy, the egg and sperm cells of the parents are changed for the purpose of passing on the changes to their offspring.

There are basically two ways of implementing a gene therapy treatment

1. Ex vivo, which means “outside the body” – Cells from the patient’s blood or bone marrow are removed and grown in the laboratory. They are then exposed to a virus (e.g. adeno virus) carrying the desired gene. The virus enters the cells, and the desired gene becomes part of the DNA of the cells. The cells are allowed to grow in the laboratory before being returned to the patient by injection into a vein.

2. In vivo, which means “inside the body” – No cells are removed from the patient’s body. Instead, vectors are used to deliver the desired gene to cells in the patient’s body.

3.1.10 Nutrigenomics- a new era in personalized functional/health foods

Nutrigenomics is the new emerging era in the development of third generation of health/functional foods and is expected to revolutionize wellness and disease management across the world. Nutrigenomics and nutrigenetics encompass the understanding of how nutrients affect health at molecular level within the body and how these effects vary between individuals. The key technologies underlying nutrigenomics address these two overlapping areas. Firstly, genomics including approaches such as DNA micro-arrays and RT-PCR which examine the interventions between nutrients and gene expression and proteomics which determine the outcome of the altered protein synthesis, activation and regulation. Both genomics and proteomic approaches examine the molecular mechanisms of nutrients, identify potential targets for nutritional interventions and establish suitable health biomarkers and their up and down regulation for monitoring the responses. Secondly, the characterization of Single Nucleotide Polymorphisms (SNPs) promises an understanding of differences in response of individual nutrients at genetic level. As the field of nutrigenomics grows with the availability of complete human genome project as public domain, it will eventually be possible for an individual to be genetically profiled, and identifying a food he should be eating or avoiding and which dietary supplement, he should be taking, that in fact is the concept of personalized foods. Very soon need based customized health foods with specific bioactive functions intended for the target population will appear at the counters in the super markets and food outlets. This effort, however, will require a strong proactive synergy between Food and Pharmaceutical industry as well as Nutritionists, Biotechnologists on one side and Dietetic and Medical professionals on the other.

Due to rapid advancements in molecular biology and powerful biotechnological tools such as second and third generation sequencing, stem cell technology, organ cloning, transgenics, pharmaco and nutrigenomics, gene therapy etc, biotechnology is going to be the most sought after technology in the next millennium to address all the problems confronting human life effectively and hence could play a significant role in poverty alleviation and improving the living standard of our vast population.

Further Reading

Books

Basic Biotechnology, 2^nd Edition Colin Ratledge and Bjorn Kristiansen (Eds), Cambridge University Press, ISBN: 0521779170

Introduction to Biotechnology Brown, C.M., Campbell, I and Priest, F.G. Panima Publishing Corporation, 2005. ISBN : 81-86535-42-X

Introduction to Biotechnology, 2^nd Edition Thieman, W.J and Pallidino, M.A. (Eds) New York : Pearson, 2009
ISBN : 978-0-321-58903-3

Internet Resources

en.wikipedia.org

biotechnologyhelp.com

www.northcarolinalifescience.com

www.bloomsburyacademic.com

www.brad.ac.uk