Microscopic membranous vesicles floating outside of cells were first discovered 50 years ago; 30 years later, a subset of these was coined exosomes. At the time, these membrane bubbles were believed to be nothing more than a cellular waste disposal mechanism. But within the past decade, extracellular vesicles – and exosomes in particular – have piqued scientists’ interests, resulting in a research boom.
In 2006, there were just 115 publications referencing exosomes; by 2015, this number had mushroomed to 1010. Today, a PubMed search brings up more than 7500 publications. Consulting firm Grand View Research estimates that the global exosome market could reach $2.28bn by 2030.
Advancements in exosome research could lead to breakthroughs in prostate cancer treatment.
The interest in exosomes has been driven by the new finding that exosomes are more than just a waste disposal system – they are also a means of communication between cells and have the ability to carry cargos such as proteins and mRNA, suggesting there could be potential medical applications.
‘Currently, research into exosomes and other extracellular vesicles is very strong,’ says Jason Webber, Prostate Cancer UK research fellow in the Division of Cancer and Genetics at Cardiff University. ‘I think this field of research will continue to grow and I believe we’ll also see greater clinical application of exosomes and a drive towards research exploring the therapeutic potential of exosomes.’
Exosomes in Cancer Research. Video: Thermo Fisher Scientific
Exosomes are best described as extracellular vescles – essentially membrane sacs – formed by the inward budding of the membrane of intracellular compartments known as multivesicular bodies (MVBs) or multivesicular endosomes (MVEs). They are released from cells when MVBs fuse with the cell’s plasma membrane, releasing its contents outside the cell. These vesicles, made of a phospholipid bilayer and ranging between 40nm and 150nm in diameter, are found in all biological fluids including blood, urine, saliva, bile, semen and breast milk.
A new type of wheat, chock full of healthy fibre, has been launched by an international team of plant geneticists. The first crop of this super wheat was recently harvested on farms in Idaho, Oregon, and Washington state in the US, ready for testing by various food companies.
Food products are expected to hit the US market in 2019. They will be marketed for their high content of ‘resistant starch’, known to improve digestive health, be protective against the genetic damage that precedes bowel cancer, and help protect against Type 2 diabetes.
How do carbohydrates impact your health? Video: TED-Ed
‘The wheat plant and the grain look like any other wheat. The main difference is the grain composition: the GM Arista wheat contains more than ten times the level of resistant starch and three to four times the level of total dietary fibre, so it is much better for your health, compared with regular wheat,’ says Ahmed Regina, plant scientist at Australian science agency CSIRO.
Starch is made up of two types of polymers of glucose – amylopectin and amylose. Amylopectin, the main starch type in cereals, is easily digested because it has a highly branched chemical structure, whereas amylose has a mainly linear structure and is more resistant.
Bread and potatoes are foods also high in starch. Image: Pixabay
Breeders drastically reduced easily digested amylopectin starch by downregulating the activity of two enzymes, so increasing the amount of amylose in the grain from 20 to 30% to an impressive 85%.
The non-GM breeding approach works because the building blocks for both amylopectin and amylose starch synthesis are the same. With the enzymes involved in making amylopectin not working, more blocks are then available for amylose synthesis.
‘Resistant starch is starch that is not digested and reaches the large intestines where it can be fermented by bacteria. Usually amylose is what is resistant to digestion,’ comments Mike Keenan, food and nutrition scientist at Louisiana State University, US. ‘Most people consume far too little fibre, so consuming products higher in resistant starch would be beneficial.’
He notes that fermentation of starch in the gut causes the production of short-chain fatty acids such as butyrate that ‘have effects throughout the body, even the mental health of humans’.
The GM wheat will hit US supermarkets in 2019. Image: Pxhere
The super-fibre wheat stems from a collaboration begun in 2006 between French firm Limagrain Céréales Ingrédients, Australian science agency CSIRO, and the Grains Research and Development Corporation, an Australian government agency.
This resulted in a spin out company, Arista Cereal Technologies. After the US, Arista reports that the next markets will be in Australia and Japan.
Large-scale industrial mining of asbestos began towards the end of the 19th Century; predominantly in Russia, China, Kazakhstan, and Brazil.
This relatively cheap material with excellent fire and heat resistance, good electrical insulating properties, and high-tensile strength was used widely in the construction industry and in many other products, including brake pads, hair dryers, and industrial filters for wine, beer and pharmaceuticals. Worldwide, an estimated two million tons of asbestos is used annually.
But asbestos exposure can be deadly. Anyone who handles the material or breathes in its fibres puts themselves at risk of lung diseases, such as asbestosis or cancer. The World Health Organization estimates that in a single year over 100,000 deaths are due to asbestos-related diseases.
Lung asbestos bodies after chemical digestion of lung tissue. Image: Wikimedia Commons
‘The truth is that it is a nasty, hazardous, toxic, carcinogenic material that has made millions and millions of people sick,’ says Arthur Frank, Professor of Environmental and Occupational Health at Drexel University, Philadelphia, US. Frank is a longtime advocate for banning the mineral.
To date, around 60 countries have banned the use of asbestos, including the UK. Russia, India, and China, however, still use asbestos in a range of products. The US is the last among developed countries not to ban asbestos entirely. More significant for Western countries are the millions of tonnes of asbestos left in buildings – asbestos becomes a problem if disturbed, especially if the fibres go undetected.
Asbestos is a health risk to construction workers. Image: Pixabay
Traditionally, those who work in the building trade are most at risk, though workers can bring home fibres on their clothes, which poses a risk to anyone they come into contact with.
‘There is a significant amount of data that points to as little as one day of exposure being sufficient to give rise to malignancy in humans and animals,’ says Frank. It’s unclear precisely the cellular mechanism, he says, but health experts agree that asbestos poses a severe public health risk. In the UK, asbestos is responsible for half of work-related cancer deaths.
The European Parliament was one of the first to ban all future asbestos use. Image: European Parliament@Flickr
The European Parliament has pushed for the removal of asbestos from all public buildings by 2028. The asbestos industry, however, argues that it is wrong to say that any exposure to asbestos can kill and believes there is a permissible level of exposure.
In the US, asbestos-related litigation is increasingly common. ‘The companies put up a fight in most cases, delaying settlement until practically the eve of trial and disputing everything they can as to medical diagnosis and causation, and evidence of the plaintiffs’ exposure histories,’ says Barry Castleman, an environmental consultant who has spent 40 years working on asbestos as a public health problem.
However, man-made substitutes for asbestos-based construction materials are available. For over 50 years, asbestos was combined with cement in Europe because its fibres are mechanically strong and durable, says Eshmaeil Ganjian, Professor of Civil Engineering Materials at Coventry University, UK.
PVA is also widely used in glue. Image: Pixabay
These boards were used for internal and external walls as well as for roofs. Europe now uses polyvinyl alcohol – widely known as PVA - in its cement boards, Ganjian says, but this is more expensive than asbestos, which has come down in price over the past 20 years.
Waste not, want not
Ganjian is currently working on a project aimed at replacing asbestos in cement boards in Iran with waste plant fibres, such as Kraft pulp, and polymeric fibres such as acrylic and polypropylene fibres. ‘The idea is to use locally available fibres, so we use cheap acrylic fibres available from petrochemical companies in the region. The strength of cellulose fibres is lower than asbestos fibres, but when we add polypropylene or acrylic or other synthetic fibres then this increases the mechanical strength,’ he explains.
Shiraz, Iran. Image: Wikimedia Commons
The Iranian government subsequently stopped importing asbestos from Russia and banned its use in cement board factories, switching to local alternatives. ‘This was a win-win situation. It saves lives and uses a waste material,’ says Ganjian.
The next five years will be the most promising in the fight against cancer with immunotherapies – such as CAR-T and moderating T-Cell approaches, and innate immunity therapies – delivering far better patient outcomes.
In the last five years, the industry has rapidly advanced its understanding of the body’s immune response and genetic markers. As a result, combination therapies – chemotherapies will continue to play an important role – are forecast to become an increasingly standardised treatment, with pharma keen to invest.
These newer options are bringing in transformative remission rates, and check-point inhibitors have already been seen to elicit long-term cures in patients, with success rates two-to-three times higher than standard chemotherapy approaches.
Over the next ten years, we will see significant breakthroughs as the industry’s understanding of the immune system improves. There are currently more than 130 biotechs – in addition to 20 big pharma companies – working on new therapies and it is believed the smaller companies are more aggressively bringing newer innovations to market. In the long run, pharma will undoubtedly absorb the most promising players in an effort to become leaders in combination therapy approaches, which many argue will deliver the best outcomes.
The current investor frenzy is comparable to that of the genomics industry at the turn of the century. Experts argue that a more complete understanding of the genome and promise of clinical data of these transformative modalities will create a golden age for cancer therapy over the next few years.
There are, however, a number of immediate challenges. For example, CAR-T, although demonstrating good efficacy in blood cancers, has yet to show enough efficacy in solid tumours. Another challenge is how far towards cures for all patients we can get, particularly for patients with late stage metastatic cancer.
Immunotherapies are moving cancer from treatment options that simply extend life or improve experience to more effective cures. The cost of newer therapies is also coming into focus; however, this is a positive pressure on companies to produce significant, not just incremental, outcomes for patients.
CRISPR/Cas9 is a gene editing tool that is swiftly becoming a revolutionary new technology. It allows researchers to edit the genome of a species by removing, adding or modifying parts of the DNA sequence.
To alter DNA using CRISPR, a pre-designed sequence is added to the DNA using a RNA scaffold (gRNA) that guides the enzyme Cas9 to the section of DNA that scientists want to alter. Cas9 ‘snips’ the selected sequence.
At this point, the cell identifies the DNA as damage and tries to repair it. Using this information, researchers can use repair technology to introduce changes to the genes of the cell, which will lead to a change in a genetic trait, such as the colour of your eyes or the size of a plants leaf.
Cas9 unzips the selected DNA sequence as the latter forms bonds to a new genetic code. Adapted from: McGovern Institute for Brain Research at MIT
Public approval of genetic modification is at an all-time high, with a recent YouGov survey finding only 7% of people in the UK oppose gene editing, although there is still a way to go. Lighter regulation in recent years has allowed smaller companies and academic institutions to undertake research.
The future of farming
One of the industries that has benefited from CRISPR is agriculture. The ongoing GM debate is an example of controversial use of transgenesis, the process of inserting DNA from one species into another, spawning fears of ‘Frankenstein foods’.
Instead of creating mega-crops that out-compete all conventional plants, gene editing provides resistance to harsh environments and infections; particularly significant in the context of global food security.
Although gene-editing has been a staple of new agriculture technology for many years now, it is only recently that CRISPR has seen successful use in human disease research and resulting clinical trials.
Scientists at the Salk Institute, California, successfully removed the MYBPC3 gene, linked to a common form of heart disease, from a human embryo. The correction was made at the earliest stage of human development, meaning that the condition could not be passed to future generations.
CRISPR is also being used to study embryo development. Recently, scientists at the Francis Crick Institute, London, discovered that the gene OCT4 was vital in these early stages, although its purpose is still not fully understood. Researchers involved believe that more research into OCT4 could help us improve success rates of IVF and understand why some women miscarry.
A human embryo at day four, taken by a Scanning Electron Microscope. Image: Yorgos Nikas, Wellcome Images
CRISPR is still in the early stages and we are far from editing embryos that can be implanted for pregnancy. Many more safety tests are required before proceeding with any clinical trials, with the next step perhaps replicating the experiment on other mutations such as BRCA1 and BRCA2, the genes responsible for an increased risk of breast cancer.
Experts are confident, however, that this technique could be applied to thousands of other diseases caused by a single mutation, such as cystic fibrosis and ovarian cancers.
The benefits of gene editing are abundant. For example, we may be able to turn the tables on antibiotic-resistant bacteria or ‘super-bugs’ by engineering bacteriophages - viruses that infect bacteria - to target antibiotic resistance genes, knocking them out and allowing conventional antibiotics to work once again. Elsewhere, CRISPR could be used to modify metabolic pathways within algae or corn to produce sustainable and cost-effective ethanol for the biofuel market.
Is CRISPR ethical?
CRISPR and gene editing will revolutionise many industries, but the fear remains in many that we will slip into a society where ‘designer babies’ become the norm, and individuality will be lost.
Marcy Darnovsky, Executive Director of the Centre for Genetics and Society, said in a statement: ‘We could all too easily find ourselves in a world where some people’s children are considered biologically superior to the rest of us.’
Could CRISPR lead to a new generation of superheros? Image: Cia Gould
Dr Lovell-Badge, from the Francis Crick Institute, disagrees. ‘I personally feel we are duty bound to explore what the technology can do in a safe, reliable manner to help people. If you have a way to help families not have a diseased child, then it would be unethical not to do it,’ he said.
Genetic engineering does not have to have an all-or-nothing approach. There is a middle ground that will benefit everyone with correct regulation and oversight. With its globally renowned research base, the UK government has a great opportunity to encourage genetic experiments and further cement Britain’s place as the genetic research hub of the future.