The sciences behind the rise of biotechnology
A collection of information and resources about some of the technologies helped build biotechnology into one of the most important tools in our lives today.
In 2016 the American Society of Clinical Oncology nominated immunotherapy as one of the most significant medical breakthroughs for cancer. How does cancer immunotherapy work? Cancer immunotherapy is designed to induce, enhance, or suppress the body’s immune system to combat tumours by using the body’s own properties, or cells grown in the laboratory. Such therapy takes two different forms. The first, known as active immunotherapy, aims to stimulate the immune system, and the second, known as passive immunotherapy, aims to strengthen the cancer patient's immune system. Immunotherapy is achieved through a number of different approaches. These range from re-activating a switch in immune cells that tumour cells turn off to prevent their own destruction, to tagging cancer cells for their elimination by immune cells, or genetically modifying a patient’s own T cells, the foot soldiers of the immune system, to directly destroy cancer cells. Immunotherapy developed on the back of knowledge accumulated from the early development of vaccines and serum therapies for infectious diseases.
CRISPR-Cas 9 is one of the newest tools for gene editing. Its development is paving the way to the insertion and removal of DNA within the genome on an unprecedented scale and at relatively small cost. The flexibility and efficiency of the technology promises to open up a new era in biotechnology and medicine.
DNA, or deoxyribonucleic acid, is a long stringy molecule that carries the genetic instructions necessary for all living organisms to grow, develop, function and reproduce. The discovery of its structure and function underpins many of the recent advances that have been made in understanding the molecular cause of disease and the formulation of new avenues of treatment.
DNA extraction is the process by which a cell is broken open to expose and extract its DNA. This is done by breaking down and emulsifying the fat and proteins that make up the cell's membrane through the addition of both salt and detergent solutions. Then the DNA is separated by by adding alcohol and centrifuging the resulting solution.
DNA polymerase is a type of enzyme that can be found in all living organisms. There are many types of DNA polymerase. Some help replicate DNA when a cell divides and others help in the day-to-day repair and maintenance of DNA. Each differ in size and shape but they all share a common structural framework. DNA polymerase is pivotal to many different forms of biotechnology. It is particularly important for performing DNA sequencing and an intrinsic component of PCR, a laboratory technique that makes it possible to make billions of copies of DNA.
DNA sequencing determines the exact order of the building blocks (nucleotide bases) in a strand of DNA. Such knowledge is important for understanding the essential genetic makeup of an organism. The technique was used in the Human Genome Project and is used for a diverse range of applications including comparative genomics and evolution, forensic science, epidemiology, medical diagnosis and the development of drugs. It is at the forefront of helping to work out the association between gene variants and physical and behaviour traits and pinpoint the cause of certain genetic diseases.
Epigenetics is one of the hottest research topics in biomedical science today. It seeks to understand how genes are switched on and off. Controlled by different chemical tags that latch on to DNA and its associated proteins, this process helps explain how cells can interpret the genetic code in different ways. Such chemical modifications are key to regulating gene expression, the process that dictates the production of proteins, the workers of the cell. Epigenetic changes underpin normal cellular development and help differentiate one type of cell from another. Any disruption to this process can cause disease. For this reason epigenetics now lies at the heart of personalised medicine.
Faecal microbiota transplant
Faecal microbiota transplantation involves the transfer of a faecal suspension containing microbiota from a healthy donor into patients with diseases caused by disturbances to their gut microflora. First described by a Chinese doctor back in the fourth century, FMT is now attracting a great deal of medical attention for the treatment of drug-resistant bacterial infections, like Clostridium difficile, and other conditions caused by microbial imbalances, such as inflammatory bowel disease. It is also being investigated for the treatment of metabolic abnormalities like obesity and type 2 diabetes.
Gene therapy involves the insertion of one or more genes designed in the laboratory into a patient’s cells or tissues to treat a disease. Originally conceived as a treatment to correct rare genetic disorders, the method has gone on to be used as a means to re-engineer cells with characteristics to help them combat cancer or prevent their degeneration. While the promise of gene therapy has yet to be fully realised in the treatment of genetic disorders, it is now making important strides in the field of cancer immunotherapy.
Immune checkpoint inhibitors
Checkpoint inhibitors are drugs that help release the brakes cancer cells put on the immune system to prevent their destruction. This is usually achieved with an antibody which is used to block certain proteins carried on the surface of cancer cells that prevent their recognition by the immune system and hence their destruction. In 2015 Jimmy Carter, the former president of the US, announced he was free of melanoma that had spread to his liver and brain. He had improved following treatment with an immune checkpoint inhibitor drug. How do checkpoint inhibitors work? Such therapy is designed to block the biological pathways cancer cells use to disguise themselves from the immune system and prevent their destruction. Immune checkpoint inhibitors are now considered one of the most promising avenues for the treatment of advanced cancer. Their development grew out of research to understand the regulation of immune responses.
Messenger RNA (mRNA)
Now a key component in COVID-19 vaccines, mRNA was once dismissed as a viable tool for medical applications because it degrades easily in the body and was difficult to produce in large quantities. The successful development of mRNA for COVID-19 vaccines marks a major turning point for mRNA. Taking over 40 years to materialise, mRNA's potential stretches well beyond the pandemic. Pivotal to instructing cells to make proteins, mRNA offers a means to get the body to make any type of protein for therapeutic and vaccine purposes.
Derived from antibodies made naturally by the body to fight foreign invaders, monoclonal antibodies have many different applications in both healthcare and other aspects of daily life. Since their development in 1975, monoclonal antibodies have helped unravel many previously unknown disease pathways, radically transformed the accuracy and speed of diagnostics and opened up new avenues for the therapy of over 50 previously untreatable diseases.
Taking 25 years to materialise, nanopore sequencing is now one of the most promising technologies for deciphering the code of DNA and RNA. Available in portable devices, nanopore sequencing has revolutionised the process of DNA and RNA sequencing. Importantly, it enables sequencing to be carried out in remote areas with limited resources. This makes it possible to detect, track and halt the spread of pathogens responsible for infectious disease outbreaks in real-time on the ground for the first time. The benefits of nanopore sequencing were first seen in the case of the Ebola and Zika viruses and today it is a critical tool for COVID-19. A quarter of all the world’s SARS-CoV-2 virus genomes have been sequenced with nanopore devices. Nanopore sequencing also provides a means to rapidly identify and monitor bacteria resistant to antibiotics, another rising public health threat. Combating infectious diseases is just the start of the multiple possibilities nanopore sequencing offers.
Designed to accurately replicate the microenvironment and physiological conditions that cells experience in the human body, organ-on-a-chip technology offers one of the most promising avenues to reduce and replace the use of animals in biomedical science today. Coming in various shapes and sizes, the tiny chips grew out of the long history of cell culture and recent advances in tissue engineering, stem cell biology, microfluidics, chemical sensor technology and analytical chemistry. Able to be used for many different applications, where the technology is generating the most excitement is as a tool to radically cut the time and cost involved in drug discovery and development and to make the process more personalised to patients based on their genetic and gender characteristics. Beyond this, the chips have already opened up a new method to study the interaction of the human immune system and infectious pathogens like bacteria and viruses as well as how diseases like cancer spread through human tissue.
The p53 gene codes for a protein that helps regulate cell division and growth and is vital to the suppression of tumours and cancer. More than half of all cancers are linked to a deficient p53, usually caused by a genetic mutation. Due to its importance in regulating the cell cycle and inhibition of tumours, p53 has become an important target in both the diagnosis and therapeutic management of cancer.
PCR (polymerase chain reaction) denotes a process that is used to replicate DNA. The first step in PCR, known as denaturing, involves heating a DNA sample to separate its two strands. Once separated the two strands are used as templates to synthesise two new DNA strands. This is done with the help of an enzyme called Taq polymerase. Once made, the newly synthesised molecules are used as templates to generate two more copies of DNA. The two basic steps involved in PCR, denaturing and synthesis, are repeated multiple times with the help of a thermocycler, a machine that automatically alters the temperature every few minutes. Each time the process of denaturing and synthesis occurs, the number of DNA molecules doubles. This makes it possible to generate one billion exact copies of an original target DNA within a couple of hours.
Phage display is a laboratory platform that facilitates the study of protein to protein, protein to peptide, and protein to DNA interactions. The technology involves the genetic modification of bacteriophages (phages), single-stranded DNA viruses that infect bacteria so that they can display a target protein or peptide on their surface. When compiled into large libraries these phages enable the high-throughput screening of proteins to identify those which bind strongly to molecules of interest. Phage display is vital to many basic biomedical research applications and for drug discovery and pharmacology.
First used in Europe in the late nineteenth century to treat bacterial infections and kept alive in the Soviet Union, Central Europe and France when antibiotics emerged, phage therapy is undergoing a major revival in Western medicine as a result of the rise in antimicrobial resistance. The therapy makes use of bacteriophages, or phages, a virus that infects and destroys bacteria but is harmless to humans, animals and plants. Phages are one of the most abundant and diverse organisms on the planet and are dependent on bacteria to replicate which they often destroy in the process. One of the advantages of phages over antibiotics is that they only target one or a few strains of bacteria so they do not disturb beneficial microbes in the body. Bacteria also find it harder to develop resistance to them.
Plasmids are small autonomous self-replicating DNA molecules that can be found in almost all bacteria, and in some fungi, protozoa, plants and animals. Because they contain only small DNA sequences, DNA plasmids are easy to isolate and manipulate. This makes them a good delivery tool for inserting foreign genes into organism, a process that is critical to producing recombinant DNA and multiplying genes of interest. They are also used to develop DNA vaccines.
Recombinant DNA is an artificial form of DNA that cannot be found in natural organisms. It is made in the laboratory by joining together genes taken from different sources. This is done by selecting and cutting out a gene at a specific point on a strand of DNA using restriction enzymes which act as molecular scissors. The gene is chosen on the basis of its ability to code for or alter different traits in another organism. It is inserted into a circular piece of bacterial DNA, called a plasmid, or a bacterial virus, called a phage, and then put into a host organism, such as the bacteria Escherichia-Coli, for replication by its cell machinery.
Restriction enzymes, also called restriction endonucleases, are DNA cutting enzymes that bacteria produce as part of their defence mechanism to prevent their destruction by invading viruses, known as bacteriophages. Such enzymes splice DNA into small fragments at specific sites in a sequence. Since the early 1970s restriction enzymes have become one of the most important tools for cutting and pasting DNA segments for different biotechnology purposes. They are particularly important for making recombinant DNA.
Stem cells are some of the body's master cells which have the ability to grow into any one of the body's more than 200 cell types. Such cells contribute to the body's ability to renew and repair its tissues. There are different types of stem cells. The first, known as embryonic stem cells, are sourced from embryos formed during the blastocyst phase of embryonic development, which is four or five days after fertilisation. They are usually taken from human embryos left-over from in vitro fertilisation. The second, known as adult or mesenchymal stem cells, are found in different types of tissue, including bone marrow, blood, blood vessels, skeletal muscles, skin and the liver. Stem cells can also be sourced from umbilical cord blood.
The human microbiome
Microbes that live on and in the human body have fascinated scientists ever since they were first observed in the 17 century. In the early days these microbes were characterised by examining their shapes, growth patterns and biochemical profiles under a microscope. All this changed with the arrival of DNA sequencing and new molecular techniques in the late 1970s, which opened up the ability to study microbial diversity and the effect of microbe on health on an unprecedented scale. Today the genes of microbes that inhabit the human body, the human microbiome, are now believed to be more essential to human health and survival than human genes.
Transgenic animals are those that have had their genes deliberately altered to give them specific characteristics they would not otherwise possess naturally. Such genetically modified animals play a pivotal role in determining the genetic cause of disease and the discovery and testing of new treatments.
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