Biotechnology
Biotechnology is…
“…[the] use of biological processes, organisms, or systems to manufacture products (or processes) intended to improve the quality of human life.”
– Professor Case
Biotechnology began all the way back during the 1970s (the capacity to clone genes was developed then). There is also evidence that biotechnology began 4000 years ago with fermentation (e.g., cheese, soy sauce, yoghurt, beer, wine, fermented spirits, etc).
As of the time of writing, there are more than 300 biologics in clinical trials targeting more than 200 diseases: COVID-19, cancers, Alzheimer’s disease, heart disease, diabetes, multiple sclerosis, AIDS, and arthritis.
There are several industries that rely on microbial biotechnology:
Bioremediation
This includes activated sludge and degrading xenobiotics.
Research
…including Taq polymerase, restriction enzymes, CRISPR, and plasmids.
Food and Beverages
This is the case for fermented food products (e.g., vinegar, wine, yoghurt, kimchi, etc).
Agriculture
GMO crops and Biopesticides are part of this.
Energy Production
This includes biofuels and microbial fuels.
Chemistry
Polymer and fine chemical production also uses microbial technology.
Sensors
This is especially the case for ecotoxicology.
Nutrition
Such technology is used here for the production of vitamins, anti-oxidants, co-factors, amino acids, and proteins.
Medicine
More than 50% of all drugs come from microbial technology. Such technology can also yield insulin, growth hormones, and vaccines.
Medicine and Pharmaceuticals
In 2006, the pharmaceutical industry was worth 650 billion USD - the industry was worth 816 billion USD in 2016.
The biologics industry grew from 63 billion USD to 163 billion USD from 2006 to 2016.
The growth of the above two industries were primarily driven by monoclonal antibodies.
Monoclonal antibodies revolution
These were the best-selling drug across the globe in 2016 (i.e., Humira) - these antibodies have applications primarily in cancer and immunomodulation.
The anti-TNF (i.e., anti-tumor necrosis factor) monoclonal antibody was worth 16 billion USD and suppresses the physiologic response of the tumor necrosis factor (responsible for causing diseases like Crohn’s disease, plaque psoriasis, and rheumatoid arthritis).
Nivolumab (i.e., BMS) and anti-PD1 monoclonal antibodies are also used to treat metastatic melanoma.
There are currently monoclonal antibodies being clinically developed against P. aeruginosa.
Insulin
Prior to the 1980s, insulin was harvested from the pancreas of cows and pigs - 23500 animals were needed to yield about one pound of insulin!
In the 1980s, microbial technology was able to produce human insulin via recombinant technology in E. coli. This was because the bacterium was able to uptake and express foreign genes!
Furthermore, E. coli has a short generation time - this enabled the rapid production of insulin and other organic compounds (e.g., biologics).
Pros and cons of E. coli production
Some pros include:
- Little to no risk of animal contamination
- Product is identical to human insulin
- Not limited by animals
Some cons include:
- LPS (i.e., lipopolysaccharide toxicity)
- Bacteria are missing the post-translational modification machinery needed to assemble the two chains of insulin.
Insuling production using yeast
This was a method pioneered by Novolin in 1987. While smaller batches of yeast can be rather expensive, there are still several pros to this method:
- No LPS are present
- A continuous culture is possible
- Insulin is secreted in the culture medium
- Mature forms (i.e., there is no need for enzymatic processes after production) can be purified and extracted.
Human Microbiota
The amount of microbes in the human body outnumber all cells by a ratio of 10 to 1. The human microbiota refers to the ecological community of microorganisms found on and in humans.
Nevertheless, microbes can also be used as a source of medicine - metagenome-wide association studies (i.e., MWAS) has revealed that certain bacterial gene families are associated with specific metabolic health states (e.g., obesity, type II diabetes).
Hence, the alteration of the microbiome is an alternative way of treating chronic disorders!
Fiber, short chain fatty acids, and immunity
Dietary fiber content influences the richness and the diversity of the gut microbiota. The fermentation of dietary fibers releases short chain fatty acids (mainly acetate, butyrate, propionate) that diffuse into the body’s circulation.
Dietary fibers also the formation of blood contents and dendritic cell components to activate helper cells in the lung.
Propionate activates signals through the GRP41 receptor, thereby protecting against allergic airway inflammation (i.e., AAI).
Butyrate is thought to be critical in the treatment against irritable bowel syndrome (i.e., IBS).
Microbiota transplants
Amazingly, 16s rRNA gene sequencing reveals small, yet significant differences in the gut microbiota between obese and lean individuals.
Hence, gut microbiota transplant is an alternative, economic option for individuals who are unable to lose weight by lifestyle options or are unable to go under the knife (for medical reasons).
Such transfer involves the transfer of microbes from a healthy human gut; this is still an active area of research (i.e., bacterial species and / or metabolites that can restore metabolic disorders first need to be identified)!
PKU and commensal bacteria
Polyketonuria (PKU) is an autosomal recessive condition that results in the abnormal metabolism of the amino acid phenylalanine.
In a healthy individual, the enzyme phenylalanine hydroxylase (i.e., PAH) converts phenylalanine to tyrosine; however, this conversion is inhibited in individuals with PKU. Consequently, phenylalanine becomes converted into phenylpyruvic acid, thereby causing (potentially fatal) mental and health defects in the patient.
The engineering of metabolic circuits in E. coli Nissle (i.e., a commensal) has been shown to degrade phenylalanine before it gets to the body’s bloodstream. Such biotics will also blend in with the gut flora and perform metabolic functions.
Wastewater Management
Bioremediation is the usage of microorganisms to clean up a contaminated environment (i.e., an environment contaminated with pathogens, nutrients, heavy metals, dissolved inorganics, biodegradable organics, etc.) - this technique is often used in wastewater management as well!
Water is a potential common source of infectious diseases (e.g., cholera) and a source for chemically-induced intoxications. Hence, ensuring water purity is essential for public health!
Primary and secondary wastewater treatment
Wastewater is liquid industrial waste or domestic sewage - gray water is water that comes from washing, bathing, and cooking. Sewage refers to water that has been contaminated with human and animal fecal material.
Hence, wastewater treatment relies on the industrial-scale usage of microbes for bioconversion. The treated wastewater is then suitable to be released into surface waters and into drinking water purification facilities.
Differences between primary and secondary wastewater treatment
Primary treatment refers to physical separation methods to separate solid and particulate (in)organic materials from wastewater.
Secondary treatment utilizes digestive reactions carried out by microbes under aerobic conditions to treat wastewater with low levels of organic materials.
Chlorination is used in most treatment plants to reduce the possibility of biological contamination.
Activated sludge
The sludge is located in the aeration tank of the treatment facility - the tank includes suspended growth processes and uses a biological floc of bacteria, protozoa, and fungi (the floc will settle in the sedimentation tank).
The aforementioned microbes conver organic matter to CO2, H2O, NH4+, and new biomass.
The aeration tank is also capable of degrading pollutants (including organic compounds, toxicants, and xenobiotics).
Challenges of wastewater treatment
First, the treatment plant is centralized, so waste must be transported to the plant in some way. There is also a large carbon footprint and capital cost involved in setting up a plant.
Treatment plants also smell bad, leave phosphate residuals, result in solids disposal, and also have a black-box system.
Furthermore, new biologically-active substances are being released into treated or untreated sewage (e.g., pharmaceuticals, personal care prducts, household products, and sunscreens) - new treatment systems will need to find a way to degrade these chemicals.
Membrane bioreactors are the next part of wastewater treatment!
