From genome mining and green synthesis, to tackling tuberculosis and computational methods to help cure malaria, the chemists of tomorrow have been busy showcasing their talents as part of the Society of Chemical Industry Young Chemists Panel’s National Undergraduate Online Poster Competition 2021.

A snapshot of these students’ talents is bottled below in their own words. So, which one of these 15 entries do you think contains the most potential?

1: Genome mining for myxobacterial natural products discovery

Emmanuelle Acs et al., University of Glasgow

Natural products have always had a privileged place in drug development programmes, but their discovery is long and tedious. Genome mining arises as a solution allowing the finding of compounds never seen before. Using an array of bioinformatic softwares, the myxobacterial genome was explored for new Ribosomally and Post-Translationally modified Peptides (RIPPs). Myxobacteria are soil-dwelling bacteria known for the number of secondary metabolites they produce, and they have proven to hide many more within their genome. Indeed, our analyses have led to the potential discovery of nine new myxobacterial natural products. The nature and class of these products is to be confirmed by biosynthesis in the laboratory.

2: De novo design of a lanthanide-binding peptide inspired by the methanol dehydrogenase enzyme active site

Olivia Baldwin et al., University of Birmingham

Lanthanides were thought to be biologically irrelevant until the discovery of bacteria containing the lanthanide-dependent methanol dehydrogenase (Ln-MDH) enzyme. There has been interest in exploiting the attractive properties of the lanthanides by the de novo design of artificial proteins, aiming to explore protein structures and functions not observed in biology. Here, a lanthanide-binding peptide, CS1-0, has been designed de novo and shown to bind to europium and pyrroloquinoline-quinone (PQQ), a key component of the Ln-MDH active site. This partial recreation of a biologically relevant lanthanide binding site is a step towards the ultimate goal of de novo design, to create functional artificial metalloproteins with simplified structures.

3: Template-directed synthesis of porphyrin nanorings: a computational and experimental study

Janko Hergenhahn et al., University of Oxford

Template-directed synthesis provides a route to achieve porphyrin nanorings by favouring ring-closure reaction over oligomerisation. A structurally new template with 12 binding sites has been proposed for the synthesis of novel porphyrin rings; however, initial unsuccessful reactions have raised questions about the binding efficiency of this template to the linear substrate. We have employed classical and quantum modelling together with experimental techniques to explore template-substrate binding in solution and shed light on this process. Titration experiments and modelling have enabled us to study the occupancy of different binding sites and quantify the influence of strain on binding, further guiding novel designs.

4: Transborylation enabled boron-catalysed hydrocyanation of enones

Kieran Benn et al., University of Edinburgh

Hydrocyanation offers an orthogonal route to synthetically ubiquitous amines. Current hydrocyanation methodologies are dominated by the use of acutely toxic hydrogen cyanide gas and transition metal catalysts. Here the application of main-group catalysis and transborylation is reported for the formal hydrocyanation of functionalised alkenes. The catalytic protocol was optimised and applied to a broad range of substrates (20 examples), including examples where chemoselectivity was demonstrated in the presence of reducible functionalities and Lewis basic groups. Mechanistic studies support a proposed catalytic cycle in which B–N/B–H transborylation was a key to catalyst turnover.

Students at the University of Glasgow have used computational analysis to help tackle malaria.

5: Investigation of the structure-property relationship between hydrophobicity and the antimicrobial activity of AMP-mimic copolymers

Xiyue Leng et al., University of Birmingham

Antimicrobial peptides are increasingly employed as new-generation antibiotics, with their amphiphilic nature (contain both hydrophobic and cationic components) mimicked by polymers to enable a more cost-effective approach. However, there is a lack of a quantitative pre-experiment indicator to provide a prospect on their potency. The overall hydrophobicity represented by LogP/SA was proposed to rapidly identify candidates in future designing to reduce synthetic efforts. We show a comparison study between two computational tools used to calculate LogP/SA: ChemBio3D and Materials Studio, in terms of the predictive power and sensitivity, followed by the synthesis of copolymers with a different cationic side chain based on the calculation results.

6: Modelling potential SARS-CoV-2 VIRTAC warheads

Mirjam-Kim Rääbis et al., University of Glasgow

Traditional small molecule therapeutics in medicinal chemistry often require high doses to inhibit the target protein, leading to issues with safety and drug resistance. Proteolysis targeting chimeras (PROTACs) are a new class of molecule that combat these issues, as they can use the body’s own protein degradation systems to degrade targets even at low drug doses. Virus-targeting chimeras (VIRTACs) can use a similar mechanism to target viral proteins. This project uses molecular docking studies to explore potential VIRTAC warheads that target the papain-like protease of SARS-CoV-2, in an attempt to find a potential treatment to COVID-19 that would, among other benefits, offer a lower risk of antiviral resistance.

7: Design, synthesis and biological evaluation of anti-tubercular small molecules

Miriam Turner et al., Newcastle University

Tuberculosis remains one of the top 10 causes of death worldwide, therefore there exists an unmet clinical need for new and improved therapeutics that tackle increasing bacterial resistance and affordability issues. Previous studies indicate N-substituted amino acid hydrazides exhibit good activity against several strains of Mtb. Ongoing structure-activity relationship studies utilising isoniazid, a variety of amino acids, and the active imidazo[1,2-a]pyridine-3-carboxy moiety of clinical candidate Q203 have also demonstrated excellent activities. Herein we report the results of our continued evaluation of this architecture, using a scaffold hopping approach to explore the potential of this pharmacophore as a new anti-tubercular drug.

8: Towards a cure for malaria: computational analysis and design of PfCLK3 inhibitors

Skye Brettell et al., University of Glasgow

Malaria continues to pose a significant challenge to humanity. Resistance to several frontline antimalarials represents a considerable threat, marking the need for new drugs with novel mechanisms of action. Kinase inhibitors represent a potential new class of antimalarials. TCMDC-135051 is a hit compound with activity against malarial kinase PfCLK3 as well as potency in liver, blood and sexual stage parasites. During this project, sequential analysis of the PfCLK3 catalytic domain identified key structural differences between the target and its human orthologs. Molecular docking studies of TCMDC-135051 analogues using GOLD then yielded potential lead compounds with predicted high affinity for the target kinase.

9: Mind the gap! Through-space electronic stabilisation of dynamic azaacene-extended helicene diimides

Matteo Albino et al., University of York

The strain-induced contortion of non-planar, chiroptically-active helicenes caused by fjord steric repulsive interactions is well known. Fjord-mediated planarisation, on the other hand, is far less common and has typically only been achieved via inherently strong covalent bond formation. Herein, I present the properties and density functional theory (DFT) analysis of electroactive aza[5]helicenes exhibiting unexpected through-space π-electronic stabilisation in the reduced states as a result of non-covalent fjord bonding effects. Computational modelling of optical spectra and aromatic-induced current densities reveal that lone pair-repulsive nitrogens in the fjord promote favourable ring currents and reversible helicene planarisation.

10: Mitochondria targeted metal-chelators as potential therapeutic agents against Parkinson’s Disease

Sam Andrew Young et al., Northumbria University

The synthesis of metal chelating molecules, specifically hydroxypyridones (HOPOs), have been identified as potential therapeutic agents for treating Parkinson’s Disease (PD) as bidentate ligands at the two oxygen donor atoms. These ligands are selective for ferric iron in the body, which is expected to stop the reduction of this iron accumulated in the brains of PD sufferers, hindering the Haber-Weiss mechanism from taking place in the mitochondria of the cell and preventing the associated degeneration of the cells. The lipophilicity of these HOPOs is vital to the process, allowing the molecule to transverse the blood-brain barrier, the addition of a triphenylphosphonium group on the HOPO is thought to increase therapeutic effect.

At Heriot Watt University, students have investigated the skin irritation potential of nanoclays using an IATA

11: Green synthesis of n-acetylcolchinol

Adelaide Lunga et al., Loughborough University

The aim of this project is to develop a short synthesis of N-acetylcolchinol using a greener and step-economical pathway. First, aldol condensation of 3-hydroxyacetophenone and 3,4,5-trimethoxybenzaldehye using ethanolic NaOH produced the respective chalcone. The product was reduced electrochemically in DMSO:MeOH (4:1) employing carbon electrodes and NEt4Cl to the saturated benzylic alcohol, which was converted to an acetamide via Ritter reaction using H2SO4 in MeCN. In the final step, the conditions were optimised to enable electrochemical oxidative coupling of the aromatic groups to give the desired N-acetylcolchinol. This novel four-steps reaction sequence avoids use of transition metal catalysts or toxic reagents.

12: Towards the synthesis of small-molecule probes to measure endosulfatase activity

Yi Xiao et al., University of Oxford

Human endosulfatases (SULFs) are enzymes on the cell surface and in the extracellular matrix that hydrolyse 6-O-sulfate on glucosamine units within heparan sulfate proteoglycans. SULFs are involved in growth and development, muscle regeneration and tumour growth via various signaling pathways, with untapped therapeutic and diagnostic potentials. However, profiling SULFs remains a challenge. Antibodies detect their presence, but do not indicate their activity state. The current activity assay is a global sulfatase assay and is not selective in a biological sample. We propose a novel small-molecule probe to profile SULF activity by exploiting the formation of 1,6-anhydrosugar, which can be potentially used in isolated proteins and in vitro.

13: Developing machine learning models to predict the Hansen solubility parameters

Alexander Pine et al., University of Greenwich

Solubility parameters are important for pharmaceutical formulations, paint formulations and new material development. There is a need to improve the accuracy of solubility calculations, and to be able to make rapid predictions of the solubility of new molecular structures. In this project, a range of Python plugins, and open-source codes have been used to develop a Lasso linear regression machine learning model to predict the Hansen solubility parameters (HSP) - δd, δp and δh, which represents dispersion forces, dipole-permanent dipole forces and hydrogen bonding respectively with the intention of making faster and more accurate prediction in solubility.

14: The cycloaddition between cyclononyne and mesyl azide

Alexander David Robertson et al., The University of Glasgow

This research considers computational modelling of a SPAAC reaction involving cyclononyne. DFT calculations were performed on the strain promoted reaction between cyclononyne and mesyl azide. Three low energy conformers of cyclononyne with Cs, C2 and C1 symmetry were found with similar energy. The transition structures for the corresponding cycloaddition with mesyl azide were found and the C2 conformer was the lowest in energy. Product structures were found leading to the identification of the thermodynamic product of the reaction. Distortion/interaction analysis showed that the cycloalkyne was already significantly pre-constrained to its reacting geometry.

15: The assessment of skin irritation potential of nanoclays using an IATA

Holly King et al., Heriot Watt university

Clays are natural nanomaterials consisting of mineral silicate layers. They have several functional uses in everyday life. An example of nanoclays that carry out a wide range of roles is smectites which include montmorillonite (MMT), bentonite and hectorite. These nanoclays can be used in cosmetics, altering their appearance and in pharmaceuticals as drug carriers and wound dressings. Integrated approach to testing and assessment (IATA) aim to collect all relevant data into one easy to understand format that can be used to group materials. Using an IATA dedicated to skin irritation/corrosion it was found that MMT was safe for use. However, hectorite was found to be toxic at high doses indicating that it is a possible irritant to the skin.

Many thanks to the sponsors of this year’s competition: GSK, AstraZeneca, TeledyneIsco. The event runs until 9 July, so let us know what you think of the entries on Twitter at #SCIPosterComp.

If you’d like to see these students’ full posters, go to: https://istry.co.uk/postercompetition/5/?date_example=2021-06-28

Many of us have contemplated buying a reconditioned phone. It might be that bit older but it has a new screen and works as well as those in the shop-front. I’m not sure, however, that any of us have thought of investing in a reconditioned liver – but it could be coming to a body near you.

Researchers based in São Paulo’s Institute of Biosciences have been developing a technique to create and repair transplantable livers. The proof-of-concept study published in Materials Science and Engineering by the Human Genome and Stem Cell Research Centre (HUG-CELL) is based on tissue bioengineering techniques known as decellularisation and recellularisation.

The organs of some donors are sometimes damaged in traffic accidents, but these may soon be transplantable if the HUG-CELL team realises its goal.

The decellularisation and recellularisation approach involves taking an organ from a deceased donor and treating it with detergents and enzymes to remove all the cells from the tissue. What remains is the organ’s extracellular matrix, containing its original structure and shape.

This extracellular matrix is then seeded with cells from the transplant patient. The theoretical advantage of this method is that the body’s immune system won’t rile against the new organ as it already contains cells from the patient’s own body, thereby boosting the chance of long-term acceptance.

However, the problem with the decellularisation process is that it removes the very molecules that tell cells to form new blood vessels. This weakens cell adhesion to the extracellular matrix. To get around this, the researchers have introduced a stage between decellularisation and recellularisation. After decellularising rat livers, the scientists injected a solution that was rich in the proteins produced by lab-grown liver cells back into the extracellular matrix. These proteins then told the liver cells to multiply and form blood vessels.

These cells then grew for five weeks in an incubator that mimicked the conditions inside the human body. According to the researchers, the results showed significantly improved recellularisation.

“It’s comparable to transplanting a ‘reconditioned’ liver, said Mayana Zatz, HUG-CELL’s principal investigator and co-author of the article. “It won't be rejected because it uses the patient’s own cells, and there’s no need to administer immunosuppressants.”

Extracellular matrix of a decellularised liver | Image Credit: HUG-CELL/USP

Obviously, there is a yawning gap between proof of concept and the operating theatre, but the goal is to scale up the process to create human-sized livers, lungs, hearts, and skin for transplant patients.

“The plan is to produce human livers in the laboratory to scale,” said lead author Luiz Carlos de Caires-Júnior to Agência FAPESP. “This will avoid having to wait a long time for a compatible donor and reduce the risk of rejection of the transplanted organ."

This technique could also be used to repair livers given by organ donors that are considered borderline or non-transplantable. “Many organs available for transplantation can’t actually be used because the donor has died in a traffic accident,” Caires-Júnior added. “The technique can be used to repair them, depending on their status.”

Even if we are at the early stages of this approach, it bodes well for future research. And for those on the organ transplant list, a reconditioned liver would be as good as a new one – complete with their very own factory settings.

Read the paper here: https://www.sciencedirect.com/science/article/abs/pii/S0928493120337814

Galen (129-216 CE) is one of the most famous and influential medical practitioners in history but he was also a scientist, an author, a philosopher, and a celebrity. He wrote hundreds of treatises, travelled and studied widely, was the physician to three emperors, and left a legacy of scientific thought that lasted for fifteen hundred years — even today, his work has an influence.

Header image Editorial credit: Eray Adiguzel / Shutterstock.com

He grew up in Pergamum, an intellectual centre of the Mediterranean world, in a wealthy family that encouraged him to pursue academia and funded his travels to learn in the best environments available, acquiring the latest techniques in medicine and healing.

He understood that diet, exercise, and hygiene were essential for good health and put that into practice in the four years he spent working for the High Priest of Pergamum's Gladiator School. This was a high profile and high pressure role and we know he reduced the death rate dramatically in his four years there. The recommendation he got helped secure him a position in Rome, capital of the empire.

He was not popular in the city — at one point, he seems to have been chased out by the local physicians, who strenuously disagreed with his methods — but he was eventually summoned by the emperor Marcus Aurelius to be his personal physician. He was described by the emperor as, “First among doctors and unique among philosophers".

Galen; Line engraving | Credit: Wellcome Images, Wikimedia Commons

Galen continued to navigate the difficult political environment of the imperial capital and was personal physician to two more emperors, while publishing prolifically and becoming one of the most well-known figures in the Roman Empire. Much of his work is lost to us but we still know a great deal about him, including that he had a flair for showmanship and controversy.

In the Greek world where he grew up, dissections had been common — of animals and humans. In Rome, this was not the case. In fact, human dissections were banned across the empire shortly before Galen arrived in the city. Undaunted, he gave a number of public anatomical demonstrations using pigs, monkeys, sheep, and goats to show his new city what they were missing (this was one of many incidents that contributed to local dislike of his methods as well as his increasing fame).

His legacy was huge, both because he recorded and critiqued the work of others in his field and because of the huge volumes of his own observations and theories. His texts were the foundation for much of medical education in the Islamic, Byzantine, and European worlds until the 17th Century.

The ban on human dissection likely limited his progress in some areas and many of his theories have (eventually) been disproved, such as the theory of the four humours — blood, black bile, yellow bile, and phlegm — based on Hippocrates' system and elaborated, as well as the efficacy of bloodletting.

Galen observed that cataracts could be removed.

In other areas, however, he was remarkably successful. He observed that the heart has four valves that allow blood to flow in only one direction, that a patient's pulse or urine held clues to their disease, that urine forms in kidneys (previously thought to be the bladder), that arteries carry liquid blood (previously thought to be air), that cataracts could be removed from patients' eyes, among others. He also identified seven of the 12 cranial nerves, including the optic and acoustic nerves.

His focus on practical methods such as direct observation, dissection, and vivisection is obviously still relevant to modern medical research. Indeed, scientists who disproved his theories, such as Andreas Vesalius and Michael Servetus in the 16th century, did so using Galen's own methods.

The study of his work remains hugely important to the history and understanding of medicine and science, as well as the ancient world. The Galenic formulation, which deals with the principles of preparing and compounding medicines in order to optimise their absorption, is named after him.

Generally, food intake measurement relies on an individual’s ability to recall what and how much they ate, which has inherent limitations. This can be overcome using biomarkers, such as urine, which contains high amounts of data, and looks to be a promising new indicator of nutritional status.

Funded by the U.S. National Institutes of Health and Health Data Research UK, the group of scientists analysed levels of 46 different metabolites in the urine of 1,848 people in the U.S, publishing their findings in the journal Nature Food.

The team illustrated the effectiveness of using metabolites in urine as an alternative approach to obtaining information on dietary patterns. Analysing the urinary metabolic profile of the individuals, they found that the 46 metabolites in urine accurately predicted healthy / unhealthy patterns, making the link between 46 metabolites in urine, as well as the types of foods and nutrients in the diet.

 

Urine test sample 

The team believes that this technology could inspire healthy changes as health professionals could be better equipped to provide dietary advice tailored to their individual biological make-up. As Dr Isabel Garcia-Perez, author of the research also from Imperial’s Department of Metabolism, Digestion and Reproduction explained: ‘Our technology can provide crucial insights into how foods are processed by individuals in different ways.’

To build on this research, the same Imperial team, in collaboration with Newcastle University, Aberystwyth University, and Murdoch University, developed a five-minute test to measure the health of a person’s diet.

This five-minute test can reveal differences in urinary metabolites, generating a dietary metabotype score for each individual. As part of this research, 19 people were recruited to follow four different diets ranging from very healthy to unhealthy. The experiments indicated that the healthier their diet, the higher the DMS score, associating higher DMS score with lower blood sugar and a higher amount of energy excreted in the urine.

 

Heart in hands

Professor John Mathers, co-author of research and Director of the Human Nutrition Research Centre at Newcastle University said: ‘We show here how different people metabolise the same foods in highly individual ways. This has implications for understanding the development of nutrition-related diseases and for more personalised dietary advice to improve public health.’

 

March in the SCIence Garden

Narcissus was the classical Greek name of a beautiful youth who became so entranced with his own reflection that he killed himself and all that was left was a flower – a Narcissus. The word is possibly derived from an ancient Iranian language. But the floral narcissi are not so self-obsessed. As a member of the Amaryllidaceae, a family known for containing biologically active alkaloids, it is no surprise to learn that they contain a potent medicinal agent. 

Narcissus (and in particular this cultivar) are an excellent source of galanthamine, a drug more commonly associated with snowdrops (Galanthus spp.). Galanthamine is currently recommended for the treatment of moderate Alzheimer’s disease by the National Institute of Health and Clinical Excellence (NICE) but is very effective in earlier stages of the disease too. 

 

Galanthamine

Today, part of the commercial supply of this molecule comes from chemical synthesis, itself an amazing chemical achievement due to the structural complexity of the molecule, and partly from the natural product isolated from different sources across the globe. In China, Lycoris radiata is grown as a crop, in Bulgaria, Leucojum aestivum is farmed and in the UK the humble daffodil, Narcissus ‘Carlton’ is the provider.

 

Narcissus ‘Carlton’ growing on large scale

Agroceutical Products, was established in 2012 to commercialise the research of Trevor Walker and colleagues who developed a cost effective, reliable and scalable method for producing galanthamine by extraction from Narcissus. They discovered the “Black Mountains Effect” – the increased production of galanthamine in the narcissus when they are grown under stress conditions at 1,200 feet. With support from Innovate UK and other organisations, the process is still being developed. Whilst not a full scale commercial production process just yet, the work is ongoing. As well as providing a supply of the much needed drug, this company may be showing the Welsh farming community how to secure additional income from their land. They continue to look for partners who have suitable land over 1000 ft in elevation. 

The estimated global patient population for Alzheimer’s in 2010 was 30 million. It is expected to reach 120 million by 2050.  The global market for Alzheimer’s disease drugs for 2019 was US$ 2870 million. 

Yesterday was Shrove Tuesday, the traditional feast day before the start of Lent. Also known as Pancake Day, many people will have returned to traditional recipes or experimented with the myriad of options available for this versatile treat. 

But you may not realise pancakes are helping to advance medicine. Here we revisit some interesting research

The appearance of pancakes depends on how water escapes the batter mix during the cooking process. This is impacted by the batter thickness. Understanding the physics of the process can help in producing the perfect pancake, but also provides insights into how flexible sheets, like those found in human eye, interact with flowing vapour and liquids.

 

Illustration of a healthy eye, glaucoma, cataract

The researchers at University College London (UCL), UK, compared recipes for 14 different types of pancake from across the world. For each pancake the team analysed and plotted the aspect ratio, i.e. the pancake diameter to the power of three in relation to the volume of batter. They also calculated the baker’s percentage, the ratio of liquid to flour in the batter.

 

Pancake batter

It was found that thick, almost spherical pancakes had the lowest aspect ratio at three, whereas large thin pancakes had a ratio of 300. The baker’s percentage did not vary as dramatically, ranging from 100 for thick mixtures to 175 for thinner mixtures.

Co-author Professor Sir Peng Khaw, Director of the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology said; ‘We work on better surgical methods for treating glaucoma, which is a build-up of pressure in eyes caused by fluid. To treat this, surgeons create an escape route for the fluid by carefully cutting the flexible sheets of the sclera.’

‘We are improving this technique by working with engineers and mathematicians. It’s a wonderful example of how the science of everyday activities can help us with medicinal treatments of the future.’

 

Classic american pancakes 

Growing in just about the most challenging of locations in the SCIence Garden are a small group of Helleborus niger. They are planted in a very dry and shady location underneath a large tree sized Escallonia and although they struggled to establish when they were first planted (in May 2017) they are now flowering and growing well.

This plant was first featured as a Horticulture Group Medicinal Plant of the Month in December 2011 and as it is now in the SCIence garden I thought a reprise was in order.

 

Helleborus is a genus of 15 species of evergreen perennials in the buttercup family, Ranunculaceae. In common with most members of the family, the flowers are radially symmetric, bisexual and have numerous stamen.

Helleborus is the Latin name for the lent hellebore, and niger means black – referring in this species to the roots.

This species is native to the Alps and Appenines. Helleborus niger has pure white flowers, with the showy white parts being sepals (the calyx) and the petals (corolla) reduced to nectaries. As with other hellebores, the sepals persist long after the nectaries (petals) have dropped.

 

All members of the Ranunculaceae contain ranunculin, an unstable glucoside, which when the plant is wounded is enzymatically broken down into glucose and protoanemonin. This unsaturated lactone is toxic to both humans and animals, causing skin irritation and nausea, vomiting, dizziness and worse if ingested.

Protoanemonin dimerises to form anemonin when it comes into contact with air and this is then hydrolysed, with a concomitant ring-opening to give a non-toxic dicarboxylic acid.

 

Many hellebores have been found to contain hellebrin, a cardiac glycoside. The early chemical literature suggests that this species also contains the substance but later studies did not find it suggesting that either mis-identified or adulterated material was used in the early studies.

It is reported to contain many other specialized metabolites including steroidal saponins.

This plant has long been used in traditional medicine – in European, Ayurvedic and Unani systems and recent research has been aimed at elucidating what constituents are responsible for the medicinal benefit.

 

Extract of black hellebore is used sometimes in Germany as an adjuvant treatment for some types of tumour.

A recent paper* reports the results of a safety and efficacy investigation. The Helleborus niger extract tested was shown to exhibit neither genotoxic nor haemolytic effects but it was shown to have anti-angiogenetic effects on human umbilical vein endothelial cells (HUVEC), anti-proliferative effects and migration-inhibiting properties on tumour cells thus supporting its use in cancer treatment.

 

* Felenda, J.E., Turek, C., Mörbt, N. et al. Preclinical evaluation of safety and potential of black hellebore extracts for cancer treatment. BMC Complement Altern Med 19, 105 (2019) doi:10.1186/s12906-019-2517-5

Of all places to have an injection, the eyeball is probably near the bottom of anybody’s list. Yet this is how macular degeneration – the leading cause of sight loss in the developed world – is commonly treated.

 

Individuals who have macular degeneration will have blurred or no vision in the center of their visual fields (as shown above).

In the UK, nearly 1.5m people are affected by macular disease, according to the Macular Society. In its commonest ‘wet’ form, macular degeneration is caused by the growth of rogue blood vessels at the back of the eye, due to over-production of a protein called vascular endothelial growth factor (VEGF).

The blood vessels leak, causing damage to the central part of the retina – the macula – and a loss of central vision. Regular injections of so-called anti-VEGF drugs help to alleviate the problem.

As well as being time-consuming, these injections can be stressful and upsetting for sufferers, many of whom are elderly. Because the condition is prevalent among older people, it is usually referred to as age-related macular degeneration, or AMD.

However, a number of emerging treatments – including eye drops, inserts and a modified ‘contact lens’ – could spell the end of regular injections, and treat the condition less invasively.

Anatomy of the eye. Video: Handwritten Tutorials

At the same time, emerging stem cell therapy, which has reversed sight loss for two patients with the ‘dry’ form of macular degeneration, could find wider use within a few years.

Scientists are closer to developing 3D printed artificial tissues that could help heal bones and cartilage, specifically those damaged in sports-related injuries. Scaffolds for the tissues have been successfully engineered.

Small injuries to osteochondral tissue – a hard bone that sits beneath a layer of cartilage that appears smooth – can be extremely painful and heal slowly. These injuries are very common in athletes and can stop their careers in their tracks. Osteochondral tissue can also lead to arthritis over time.

 

These types of injuries are commonly seen in athletes.

As osteochondral tissue is somewhere between bone and cartilage, and is quite porous and very difficult to reproduce. But now, bioengineering researchers at Rice University, Texas, US, have used 3D printing techniques to develop a material that may be be suitable in future for medical use.

A porous scaffold, with custom polymer mixes for cartilage and ceramic for bone, was engineered. The imbedded pores allow cells and blood vessels from the patient to infiltrate, integrating the scaffold into the natural bone and cartilage.

‘For the most part, the composition will be the same from patient to patient,’ said Sean Bittner, graduate student at Rice University and lead author of the study.

In honour of World Health Day, held on 7 April 2019 annually, we have collated the five most innovative healthcare projects we have featured on SCI’s website over the past year. 

New cardiac MRI scan improves diagnostic accuracy

Using 2D imaging techniques to diagnose problems with the heart can be challenging due to the constant movement of the cardiac system. Currently, when a patient undergoes a cardiac MRI scan they have to hold their breath while the scan takes snapshots in time with their heartbeat.

Still images are difficult to obtain with this traditional technique as a beating heart and blood flow can blur the picture. This method becomes trickier if the individual has existing breathing problems or an irregular heartbeat.

3D cell aggregates could improve accuracy of drug screening

 

An innovative new screening method using cell aggregates shaped like spheres may lead to the discovery of smarter cancer drugs, a team from the Scripps Research Institute, California, US, has reported.

The 3D aggregates, called spheroids, can be used to obtain data from potentially thousands of compounds using high throughput screening (HTS). HTS can quickly identify active compounds and genes in a specific biomolecular pathway using robotics and data processing.

Antibiotic combinations could slow resistance

 

Several thousand antibiotic combinations have been found to be more effective in treating bacterial infections than first thought.

Antibiotic combination therapies are usually avoided when treating bacterial infections, with scientists believing combinations are likely to reduce the efficacy of the drugs used. Now, a group at UCLA, USA, have identified over 8,000 antibiotic combinations that work more effectively than predicted.

Mechanism that delays and repairs cancerous DNA damage discovered

 

Researchers at the University of Copenhagen, Denmark, have identified a mechanism that prevents natural DNA errors in our cells. These errors can lead to permanent damage to our genetic code and potentially diseases such as cancer.

Mutations occurring in human DNA can lead to fatal diseases like cancer. It is well documented that DNA-damaging processes, such as smoking tobacco or being exposed to high levels of ultraviolet (UV) light through sunburn, can lead to increased risk of developing certain forms of cancer.

Alzheimer’s drugs made from Welsh daffodils

Treatments for Alzheimer’s disease can be expensive to produce, but by using novel cultivation of daffodils one small Welsh company has managed to find a cost-effective production method of one pharmaceutical drug, galanthamine.

Alzheimer’s disease is a neurodegenerative disease with a range of symptoms, including language problems, memory loss, disorientation and mood swings. Despite this, the cause of Alzheimer’s is very understood. The Alzheimer’s disease drug market is currently worth an estimated US$8bn.

 

The Svalbard Islands are in Northern Norway.

The finding is all the more unexpected as the team was seeking a virgin environment to try and establish what a background level of antimicrobial resistance in soil bacteria looks like. 

 

Scientists found genes important to antimicrobial resistance in soil bacteria.

‘We took 40 samples to give us an idea of what the baseline of resistance might look like in nature, but we were surprised by how different the sites were from each other,’ says lead scientist David Graham at Newcastle University. Areas with high wildlife or human impact had greatest diversity of resistance DNA in the soil.

The results show that antibiotic resistance genes are accumulating even in the most remote locations. Included in a number of samples was a multidrug resistant gene called New Dehli strain, first isolated in India.

Newcastle University find antibiotic resistant genes in Arctic. Video: Newcastle University

Some sites had levels of antimicrobial resistance 10 times greater than others, particularly those with elevated levels of phosphorus, a nutrient usually scarce in Arctic soils. 

‘There was much greater resistance diversity in sites with strong signatures of faecal matter,’ says Graham, indicating that migratory birds most likely brought the antimicrobial resistance genes, depositing them via their guano.

 

Almost half of world’s adults aged 85 and over have Alzheimer’s Disease.

The amyloid-B precursor protein (APP) plays a key role in the development of the amyloid plaques that are the hallmark of Alzheimer’s disease. Now, researchers claim to have identified thousands of genetic variants of the APP gene that codes for the protein in the brains of patients with the most common form of Alzheimer’s disease, known as late-onset or sporadic AD (SAD). 

The study reveals for the first time how this genetic variation occurs – by a mechanism involving the enzyme reverse transcriptase, the same type of enzyme used by HIV to infect cells.

 

APP forms plaques in the brain, as shown above in a light micrograph.

Our findings provide a scientific rationale for immediate clinical evaluations of HIV antiretroviral therapies in people with AD,’ says Jerold Chun, senior VP of Neuroscience Drug Discovery at Sanford Burnham Prebys Medical Discovery Unit (SBP), an idea that the researchers say is supported by the relative absence of proven AD in ageing HIV patients on antiretroviral medication.

The APP gene variants were created by reverse transcription, the researchers note, when RNA acts as a template to form complementary DNA sequences that are then reinserted back into the original genome.

Discovery of possible Alzheimer’s treatment. Video: Sanford Burnham Prebys Medical Discovery Institute

This process of gene recombination – which occurs each time cells divide to make new ones – has not previously been reported in nerve cells (neurons) in the brain but could also help to explain the complexity and diverse functions of our brain cells.

2019 has been declared by UNESCO as the Year of the Periodic Table. To celebrate, we are releasing a series of blogs about our favourite elements and their importance to the chemical industry. Today’s blog is about the exciting group one element, lithium!

 

Lithium has a wide range of uses – it can even power batteries!

Bipolar disorder

Lithium was first discovered in mines in Australia and Chile, and was initially used to treat gout, an arthritic inflammatory condition. Its use as a psychiatric medication wasn’t established until 1949, when an Australian psychiatrist discovered the positive effect that lithium salts had on treating mania. Since then, scientists have discovered that lithium works as a mood stabiliser by targeting neurotransmitters in the brain.

Neurotransmitters are chemicals that are released by one neuron to send a message to the next neuron. There are several types found in humans including dopamine, serotonin and glutamate. Each has a different role, and different levels of each neurotransmitter can be linked to a variety of mental illnesses. However, it is an increase in glutamate – an excitatory neurotransmitter that plays a role in learning and memory – and has been linked to the manic phase of bipolar disorder.

 

Lithium salts have been used as a medication for mania effectively since 1949. Image: Pixabay

Lithium is thought to stabilise levels of glutamate, keeping it at a healthy and stable level. Though it isn’t a fully comprehensive treatment for bipolar disorder, lithium has an important role in treating the manic phase and helping researchers to understand the condition.

Battery power

One of the most common types of battery you will find in modern electronics is the lithium ion battery. This battery type was first invented in the 1970s, using titanium (IV) sulphide and lithium metal. Although this battery had great potential, scientists struggled to make a rechargeable version.

Initial rechargeable batteries were dangerous, mainly due to the instability of the lithium metal. This resulted in them failing safety tests and led to the use of lithium ions instead.

 

Lithium-ion batteries are widely used and developments in the technology continue today.

Developments in lithium ion technology continue to this day, in which the recently-founded Faraday Institute plays a large role. As part of the Faraday Battery Challenge, they are bringing together expertise from universities and industry, supporting projects that develop lithium-based batteries, along with new battery technologies.

Nuclear fusion

Nuclear fusion happens in a hollow steel donut surrounded by magnets. The large magnetic fields contain a charged gas known as plasma, which is heated to 100m Kelvin and leads to nuclear fusion of the deuterium and tritium in the plasma. Keeping the plasma stable and preventing it from cooling is one of the largest industrial problems to overcome. This is where lithium comes in.

Results from studies in which lithium is delivered in a liquid form to the edge of the plasma, show that lithium is stable and maintains its temperature and could potentially be used in controlling the plasma. It can also increase the plasma temperature if injected under certain conditions, improving the overall conditions for fusion.

Lithium has uses in plasma stabilisation in nuclear fusion. Video: Tedx Talks

Aside from its uses in nuclear fusion, lithium has other uses in the nuclear industry. For example, it is used as an additive in coolant systems. Lithium fluoride and other similar salts have a low vapour pressure, meaning they can carry more heat than the same amount of water.

Coeliac disease is caused by an autoimmune response to gluten and affects approximately 1 in 100 people worldwide. Those affected must eat a gluten-free diet, or they may experience uncomfortable digestive symptoms, mouth ulcers, fatigue and anaemia.

What’s the big deal with gluten? Video: TED-Ed

Problems occur for coeliac disease patients when they are exposed to gluten – a protein found in wheat and other grains – and the immune system is triggered to attack the body. This results in inflammation, mainly in the intestines, and causes the subsequent acute symptoms related to the condition.

Over 90% of coeliac disease patients carry immune recognition genes known as HLA-DQ2.5. These genes are human leukocyte antigen (HLA) genes, which usually relate to specific diseases.

 

ImmusanT, a leader in the development of therapies for autoimmune disorders, has developed a vaccine that targets patients carrying the HLA-DQ2.5 genes. This novel therapeutic vaccine, known as Nexvax2, works by reprogramming specific T cells that are responsible for triggering an inflammatory response when gluten is consumed.

2019 has been declared by UNESCO as the Year of the Periodic Table. To celebrate, we are releasing a series of blogs about our favourite elements and their importance to the chemical industry. Today’s blog is about one of the most abundant and most used elements, carbon!

Carbon-based life

Carbon could be called the element of life – it can be found in every living creature on Earth in a variety of different forms, from the backbone of your DNA, to the taste receptors in your tongue and the hormones controlling your hunger. Carbon-based chemistry surrounds us – in the air we breathe, in the food we eat and in the soil beneath our feet.

So, why is carbon so important to life? Carbon’s chemistry allows it to form large, intricate 3D structures, which are the basis of its interaction in biology – like jigsaw pieces that come together to build a tree, an elephant or a human being.

The study of carbon-based chemistry, or organic chemistry, has allowed us to better understand our living world and the interactions that occur, leading to development of better tasting food, higher yielding crops and more efficient medicines to improve our health. 

In the early 19th century, chemist Justus von Liebig began synthesising organic, carbon-based molecules and said: ‘The production of all organic substances no longer belongs just to living organisms.’ 

Since then, hundreds of organic compounds for medicinal use have been synthesised – from adrenaline to ibuprofen – and hundreds of unique synthesis pathways have been described.

 

Organic chemistry – the study of carbon-based chemistry – has given us hundreds of modern medicines. 

Carbon in materials

Atoms of carbon can make four bonds, each with another carbon attached, to arrange themselves into different molecular structures and form completely different substances. These molecular structures, known as allotropes, can result in vast differences in the end-result material. 

For example, one allotrope, diamond, is the hardest and highest thermally conductive of any natural material, whereas another, graphite, is soft enough to be used in pencils, and is highly conductive of electricity.

Graphene is carbon allotrope that exists in thin, 2-dimensional layers, with the carbon atoms arranged in a honeycomb formation. Scientists had theorised its existence for years, but it was not isolated and characterised until 2004 by Andre Geim and Konstantin Novoselov at the University of Manchester, UK. The pair won the 2010 Nobel Prize in Physics for their work. 

 

The structure of carbon atoms in graphene.

Graphene is a highly conductive, flexible and transparent – this means it can be used in electronics, medical biotechnology, and a variety of other innovative solutions.

Another innovative material made from carbon is carbon fibre, which can then produce carbon-fibre reinforced polymer (CFRP). CFRP is a polymer interwoven with fibres of carbon, which is 5-10μm in diameter. The mixture of these two materials gives an extremely strong but lightweight material, useful in building products from aerospace and automotive, to sports equipment and technology.

Fueling the world

The name carbon comes from the Latin carbo meaning coal, and until recently most of our energy was generated by the consumption of carbon through the burning of naturally occurring carbon-based fuels, or fossil fuels. When these fuels, such as coal, natural gas and oil, are burnt, the combustion reaction generates carbon dioxide (CO2). 

 

CO2, produced by burning fossil fuels, is thought to be a contributor to climate change. Image: Pixabay

High production of the by-product CO2, and its release into the atmosphere, is considered to have a negative environmental impact and is thought to contribute to global warming and climate change. Fossil fuels are not a renewable resource and supplies are expected to diminish in the next 50-100 years. 

Consequently, there has been a movement towards more renewable energy, from wind, solar and hydropower, driving a move towards a low-carbon economy. These energy sources are generally considered to be better for the environment, with lower amounts of CO2 being produced.

Chemical engineer Jennifer Wilcox previews some amazing technology to scrub carbon from the air, using chemical reactions that capture and reuse CO2. Video: TED

In this strive for a low-carbon economy, new technology is being used that prevents the release of CO2 into the atmosphere in the first place. Carbon capture and storage (CCS) takes waste CO2 from large-scale industrial processes and transports it to a storage facility. This CCS technology is one of the only proven, effective methods of decarbonisation currently available.

Roughly 60% of the 12 million animal experiments in Europe each year involve mice. But despite their undoubted usefulness, mice haven’t been much help in getting successful drugs into patients with brain conditions such as autism, schizophrenia or Alzheimer’s disease. So too have researchers grown 2D human brain cells in a dish. However, human brain tissue comprises many cell types in complex 3D arrangements, necessary for true cell identity and function to emerge.

Researchers are hopeful that lab grown mini-brains – tiny 3D tissues resembling the early human brain – may offer a more promising approach. ‘We first published on them in 2013, but the number of brain organoid papers has since skyrocketed, with 300 just last year,’ says Madeline Lancaster at the Medical Research Council’s Laboratory of Molecular Biology lab in Cambridge, UK.

 

Lancaster was the first to grow mini-brains – or brain organoids – as a postdoc in the lab of Juergen Knoblich at the Institute of Molecular Biotechnology in Vienna, Austria. The miniature brains comprised parts of the cortex, hippocampus and even retinas, resembling a jumbled-up brain of a human foetus.

‘We were stunned by how similar the events in the organoids were to what happens in a human embryo,’ says Knoblich. To be clear, the brain tissue is not a downsized replicate. Lancaster compares the blobs of tissue to an aircraft disassembled and put back together, with the engine, cockpit and wings in the wrong place.

Growing mini brains to discover what makes us human | Madeline Lancaster. Video: TEDx Talks  

‘The plane wouldn’t fly, but you can study each of those components and learn about them. This is the same with brain organoids. They develop features similar to the human brain,’ she explains.

Biopharmaceuticals are sourced from living organisms.

Researchers at Massachusetts Institute of Technology (MIT), US, have developed a portable drug manufacturing system that can make several different biopharmaceuticals to be used in precision medicine or to treat outbreaks in developing countries.

Biopharmaceuticals are drugs made up of proteins such as antibodies and hormones, and are produced in bioreactors using bacteria, yeast or mammalian cells. They must be purified before use, so the process has dozens of steps and it can therefore take weeks or months to produce a batch.

The Challenges in Manufacturing Biologics. Video: Amgen  

Due to the complex nature of the process and its time restrictions, biopharmaceuticals are usually produced at large factories dedicated to a single drug – often one that can treat a wide range of patients.

To help supply smaller, more specific groups of patients with drugs, a group of researchers at MIT have developed a system that can be easily configured to produce three different pharmaceuticals – human growth factor, interferon alpha 2b and granulocyte colony-stimulating factor – all of a comparable quality to commercially available counterparts.

 

Biopharmaceuticals can treat autoimmune diseases, such as arthritis. Image: Pixabay

‘Traditional biomanufacturing relies on unique processes for each new molecule that is produced,’ said J Christopher Love, a Chemical Engineering Professor at MIT’s Koch Institute for Integrative Cancer Research. ‘We’ve demonstrated a single hardware configuration that can produce different recombinant proteins in a fully automated, hands-free manner.’

The field of regenerative medicine is at a ‘pivotal point’ in its development, according to a panel of experts speaking at the Bio meeting in Boston in June 2018. 

The past six months alone saw four new product approvals, which could be the ‘beginning of a large number of successes’, said moderator Morrie Ruffin, Managing Director of the Alliance for Regenerative Medicine, which now has over 300 members.

Clinical results emerging from cell therapies over the next two years will be comparable with the successes seen with CAR-T cancer therapies, predicts Mike Scott, Vice-President of Product development at Toronto-based Blue Rock Therapeutics, whose lead product uses pluripotent stem cells to grow new neurons that restore the lost dopamine function in Parkinson’s patients.

‘The area of regenerative medicine allows us to do something audacious: to strive for cures. If you think of CAR-T and gene therapies, there’s every reason to say we can achieve the same with regenerative medicines,’ agreed Felicia Pagliuca, Co-Founder of Boston biotech company Semma Therapeutics. 

Semma aims to replace the lost pancreatic beta cells of patients with Type 1 diabetes with its insulin producing equivalents grown in the lab. The technology is currently at preclinical stage.

 

Regenerative medicine could help to treat diseases like type 1 diabetes, in which pancreatic cells function abnormally. Image: Pixabay

Storing placental and cord blood cells at birth may no longer be necessary in the future, the researchers suggested. Traditional stem cell therapy approaches have used mesenchymal stem cells from these sources to regrow tissues and organs by differentiation into multiple cell types. However, newer technologies are increasingly making new cell types from pluripotent stem cells generated directly from adult cells such as skin.

The field of regenerative medicine is at a ‘pivotal point’ in its development, according to a panel of experts speaking at the Bio meeting in Boston in June 2018. 

The past six months alone saw four new product approvals, which could be the ‘beginning of a large number of successes’, said moderator Morrie Ruffin, Managing Director of the Alliance for Regenerative Medicine, which now has over 300 members.

Clinical results emerging from cell therapies over the next two years will be comparable with the successes seen with CAR-T cancer therapies, predicts Mike Scott, Vice-President of Product development at Toronto-based Blue Rock Therapeutics, whose lead product uses pluripotent stem cells to grow new neurons that restore the lost dopamine function in Parkinson’s patients.

‘The area of regenerative medicine allows us to do something audacious: to strive for cures. If you think of CAR-T and gene therapies, there’s every reason to say we can achieve the same with regenerative medicines,’ agreed Felicia Pagliuca, Co-Founder of Boston biotech company Semma Therapeutics. 

Semma aims to replace the lost pancreatic beta cells of patients with Type 1 diabetes with its insulin producing equivalents grown in the lab. The technology is currently at preclinical stage.

 

Regenerative medicine could help to treat diseases like type 1 diabetes, in which pancreatic cells function abnormally. Image: Pixabay

Storing placental and cord blood cells at birth may no longer be necessary in the future, the researchers suggested. Traditional stem cell therapy approaches have used mesenchymal stem cells from these sources to regrow tissues and organs by differentiation into multiple cell types. However, newer technologies are increasingly making new cell types from pluripotent stem cells generated directly from adult cells such as skin.

With a rapidly increasing population, the world is struggling to meet the demand for food, water, energy, and medicine. In 2011, the global population reached 7bn – approximately the amount of grains of sand you can fit it a post box, says Sir Martyn Poliakoff – and this number has since increased.

On Wednesday 25 April 2018 at his Public Evening Lecture, Sir Martyn discussed the role of photochemistry – the study of light’s effects on chemical reactions – in creating a greener and more sustainable society as essential resources deplete.

‘Chemists have to help address the sustainability challenges facing our society,’ he said. His research group at the University of Nottingham is proving that photochemistry can make an impact.

Fighting Malaria with Green Chemistry. Video: Periodic Videos

There are 1.3bn individuals in the world who are considered ‘profoundly’ poor. To define this Sir Martyn illustrated the profoundly poor ‘can, in their head, list everything they own’.

Today, there are more people worldwide that use mobile phones than toothbrushes. As no one wants to consume less, he asked: ‘Can we provide more for the poor without robbing the rich?’

Read the full article here....

The eighth in its series, the Kinase 2018: towards new frontiers 8th RSC/SCI symposium on kinase design took place at the Babraham Institute, Cambridge – a world-leading biomedical science research hub.  

The focus of the event was to provide a space for the discussion of the ever-evolving kinase inhibitor landscape, including current challenges, opportunities and the road ahead.

A kinase is an enzyme that transfers phosphate groups to other proteins (phosphorylation). Typically, kinase activity is perturbed in many diseases, resulting in abnormal phosphorylation, thus driving disease. Kinases inhibitors are a class of drug that act to inhibit aberrant kinases activity.

Cell signalling: kinases & phosphorylation. Image: Phospho Biomedical Animation

Over 100 delegates from across the world working in both academia and industry attended the event, including delegates from GlaxoSmithKline, AstraZeneca, Genentech, and Eli Lilly and Co.

The event boasted world-class speakers working on groundbreaking therapeutics involving kinase inhibitors, including designing drugs for the treatment of triple negative breast cancer, complications associated with diabetes, African sleeping sickness and more.

How can kinase inhibitors revolutionise cancer treatment?

 

Tsetse flies carry African sleeping sickness. Image: Oregon State University/Flickr

The keynote speaker, Prof Klaus Okkenhaug from Cambridge University, spoke about how the immune system can be manipulated to target and kill cancer cells by using kinase inhibitors.

Klaus is working on trying to better understand the effects of specific kinase inhibitors on the immune system in patients with blood cancer.

He also explored how his work can benefit those with APDS, a rare immunodeficiency disorder, which he helped to elucidate on a molecular level.

Solving graft rejection, one kinase at a time

 

Organ grafts are a surgical procedure where tissue is moved from one site in the body to another. Image: US Navy

Improving tolerance to organ grafts is at the forefront of transplantation medicine. James Reuberson from UCB Pharma UK, highlighted how kinase inhibitors can be utilised to improve graft tolerance.  

James took the delegates on a journey, describing the plight of drug discovery and development, highlighting the challenges involved in creating a drug with high efficacy. While still in its infancy, James’ drug shows potential to prolong graft retention.

An innovative new screening method using cell aggregates shaped like spheres may lead to the discovery of smarter cancer drugs, a team from the Scripps Research Institute, California, US, has reported.  

The 3D aggregates, called spheroids, can be used to obtain data from potentially thousands of compounds using high throughput screening (HTS). HTS can quickly identify active compounds and genes in a specific biomolecular pathway using robotics and data processing.

 

A spheroid under a confocal microscope. Image: Kota et al./The Scripps Research Institute  

The spheroids – 100 to 600 microns thick in diameter – spread in a similar way to cancer cells in the body and are therefore more effective in identifying potential cancer drugs, the team hypothesises.

For this study, the team focused on KRAS – a gene belonging to the RAS family. It is estimated these genes account for one-third of all cancers.

 

Robots handle assays in a HTS system. Image: NIH/Flickr

DOI: 10.1038/s41388-018-0257-5

Researchers claim to be ‘on the cusp’ of creating a new generation of devices that could vastly expand the practical applications for 3D and 4D printing. At the ACS meeting in New Orleans in March, H. Jerry Qi at Georgia Institute of Technology reported the development of a prototype printer that not only simplifies and speeds up traditional 3D printing processes, but also greatly expands the range of materials that can be printed.

4D printing would allow 3D printed components to change their shape over time after exposure to environmental triggers such as heat, light and humidity. In 2017, for example, Qi’s group, in collaboration with scientists at the Singapore University of Technology and Design, used a composite made from an acrylic and an epoxy along with a commercial heat source to create 4D objects, such as a flower that can close its petals or a star that morphs into a dome. These objects transformed 90% faster than previously possible because the team incorporated the mechanical programming steps directly into the 3D printing process.

 

H Jerry Qi (right) with Glaucio Paulino, a professor at Georgia Tech’s School of Civil and Environmental Engineering, hold 3D printed objects that use tensegrity – a structural system of floating rods in compression and cables in continuous tension. Image: Rob Felt

‘As a result, the 3D printed component can rapidly change its shape upon heating,’ the researchers reported. ‘This second shape largely remains stable in later variations in temperature such as cooling back to room temperature. Furthermore, a third shape can be programmed by thermomechanical loading, and the material will always recover back to the permanent (second) stable shape upon heating.’

In their latest work, the group sought to create an ‘all-in-one’ printer that combines four different printing techniques: aerosol, inkjet, direct ink write and fused deposition modelling. The resulting machine can handle a range of materials such as hydrogels, silver nanoparticle-based conductive inks, liquid crystal elastomers and shape memory polymers (SMPs). 

It can even create electrical wiring that can be printed directly onto an antenna, sensor or other electrical device. The process uses a direct-ink-write method to produce a line of silver nanoparticle ink, which is dried using a photonic cure unit – whereupon the nanparticles coalesce to form conductive wire. Lastly, the wires are encased in plastic coating via the printer’s inkjet component.

The researchers can also use the printer to create higher quality SMPs capable of making more intricate shape changes than in the past. And to also make materials comprising both harder and softer or more bendable regions, Qi explained. Here, the printer projects a range of white, grey or black shades of light to trigger a polymer crosslinking reaction dependent on the greyscale of shade shone on the component part. Brighter light shades create harder component parts than darker shades.

In terms of applications, Qi’s own particular interest is in developing ‘soft robots’ with sensory properties more akin to human skin than the traditional metallic or rigid robots with which we are probably more familiar. Sensory robots, Qi says, will play a big role in future safety for human workers working alongside robots. As a first step in that direction, his group is currently working with Children’s Healthcare of Atlanta to investigate whether the new technology could make prosthetic hands for children born with malformed arms – a condition not covered by most medical insurance policies. The idea would be to combine multiple different sensors to create a functional replacement hand.

In future, new 3D and 4D printers will ultimately be capable of printing whatever we might want to make, Qi says. He points, for example, to work by Jennifer Lewis at the University of Harvard to 3D print a Li-ion battery – an essential component of mobile phones and computer laptops. However, Qi notes that 3D printing does not always make economic or practical sense for all items. Instead, a big consideration will be ‘pick and place’ technology that mixes and matches printed and non-printed components to assemble the desired objects.

A shortage of donor organs for transplant surgery is fueling research to develop artificial livers and hearts, but how closely do they match up to the real thing?

Liver failure due to alcohol abuse, drug overdose and hepatitis is a growing problem. In 2016, 1220 Americans died waiting for a liver transplant, with the cost of treating cirrhosis – late stage liver scarring – is estimated at nearly $10bn/year.

‘In 2017, if you have liver failure, we don’t have a backup system,’ says Fontes. ‘But my group has a potential backup system. We are not ready for prime time yet, but we’ve some really good data.’

 

Liver failure can be hereditary or caused by excessive drinking. Image: Pixabay

Transplant surgeon Paulo Fontes at the University of Pittsburgh, US, regularly meets patients who ask what their options are aside from a liver transplant.

His group has attempted to build a new bioartificial liver, by seeding liver cells onto a liver scaffold. However, others working in this area have so far met with little success.

Now Fontes, working at the Starzl Transplantation Institute, has hit on a different strategy: to grow mini livers in living organisms. The work is in collaboration with Eric Lagasse, a stem cell biologist at the University of Pittsburgh, who showed lymph nodes are excellent ‘bioreactors’ for growing different types of cells, including liver cells.

 

The liver – made up of hepatocytes – has the capacity to regenerate after surgery. Image: Ed Uthman/Flickr

Lymph nodes filter damaged cells and foreign particles out of the body’s lymph system, which transports fluids around the body. When someone is ill, T cells from the immune system move to the lymph nodes to be cloned and released back to the bloodstream en masse to take on the microbe causing the illness.

For the past five years, Fontes and Legasse have been working with large animal models, infusing hepatocytes into the lymph nodes of pigs. ‘Within two months, it is amazing, but you have mini livers in the lymph nodes,’ he explains. ‘When you compare the mini liver with normal livers, they look very similar.’

 

Pigs are common animal models as they have similar organ systems to humans. Image: Pixabay

The mini livers weigh a few grams and would not offer a complete replacement for failed livers, but rather a supplement of liver tissue in patients with end stage liver disease who are too sick to undergo a transplant.

‘A lot of these patients have significant heart and lung problems, so would not sustain a full transplant,’ says Fontes. ‘The idea is to sustain their life by increasing their liver mass by creating new small ectopic livers within their lymph nodes.’

Compared with artificial livers, artificial heart technology is much further along the road to the clinic. To date, around 2000 artificial hearts have been implanted in patients, with demand driven similarly by an acute shortage of donors.  

‘We wanted an artificial heart very similar to the natural human heart,’ explains Nicolas Cohrs at ETH Zurich in Switzerland. ‘Our hypothesis is that when you mimic the human heart in function and form you will have fewer side effects.’

Cohrs and his colleagues aim to print their artificial hearts so that they fit precisely into an individual patient. This is not yet close to clinic, but promises a tailored heart.

‘We take a CT scan of a patient, put it in a computer file and design an artificial heart around it, so it closely resembles the patient heart,’ says Cohrs. ‘We use these 3D printers and print a mould in ABS [acrylonitrile butadiene styrene], which is the plastic Lego is made of, fill it with silicone and then dissolve the mould with acetone to leave behind the silicone heart.’

Testing a soft artificial heart. Video: ETH Zurich

The plastic heart deflates and inflates with pressurised air. The first-generation device, made from silicone, has two chambers but survived for only 2000 beats. ‘This is only half an hour, so there is a lot of improvement needed,’ adds Cohrs.

A new prototype made from a more resistant [so far, undisclosed] polymer has managed more than a million beats, which is the equivalent of 10 days for a human heart. The goal is to develop a four-chamber heart that beats for 10 years, so a lot more work is still needed.

Using 2D imaging techniques to diagnose problems with the heart can be challenging due to the constant movement of the cardiac system. Currently, when a patient undergoes a cardiac MRI scan they have to hold their breath while the scan takes snapshots in time with their heartbeat.

Still images are difficult to obtain with this traditional technique as a beating heart and blood flow can blur the picture. This method becomes trickier if the individual has existing breathing problems or an irregular heartbeat.

These problems can lead to trouble in acquiring accurate diagnostics.  

 

Now, a team based at the Cedars-Sinai Medical Center in California, US, have detailed a new technique – MR Multitasking – that can resolve these issues by improving patient comfort and shortening testing time.

‘It is challenging to obtain good cardiac magnetic resonance images because the heart is beating incessantly, and the patient is breathing, so the motion makes the test vulnerable to errors,’ said Shlomo Melmed, Dean of the Cedars-Sinai Center faculty.

 

An MRI Scanner. Image: Wikimedia Commons

‘By novel approaches to this longstanding problem, this research team has found a unique solution to improve cardiac care for patients around the world for years to come.’

By developing what the team consider a six-dimensional imaging technique, the Center has embraced the motion of a heartbeat by capturing image data continuously – creating a product similar to a video.

‘MR Multitasking continuously acquires image data and then, when the test is completed, the program separates out the overlapping sources of motion and other changes into multiple time dimensions,’ said Anthony Christodoulou, first author and PhD researcher at the Center’s Biomedical Imaging Research Institute.

‘If a picture is 2D, then a video is 3D because it adds the passage of time,’ said Christodoulou. ‘Our videos are 6D because we can play them back four different ways: We can playback cardiac motion, respiratory motion, and two different tissue processes that reveal cardiac health.’

Your guide to a cardiac MRI. Video: British Heart Foundation

Testing ten healthy volunteers and ten cardiac patients, the team said the group found that the method was more comfortable for patients and took just 90 seconds – significantly quicker than the conventional MRI scan used in hospitals. For each of the participants, the scan produced accurate results.

The team are now looking to extend its work into MR Multitasking by focusing on other disease areas, such as cancer.

Around 700,000 people worldwide die every year from bacteria that have developed resistance to antibiotics. In the UK alone, that figure is at least 12,000 – more deaths than from breast cancer. And those numbers look set to rise even higher.

‘It’s not just the fact that resistance is increasing – that’s inevitable,’ says Nick Brown, Director of advocacy group, Antibiotic Action. ‘The issue is more the rate of increase in resistance, which appears to be accelerating.’

The Infectious Diseases Society of America recently reported resistance to drugs within six months of antibiotics coming onto the market, and in some cases, even before the drug goes on the market. Many bacterial strains are increasingly displaying resistance to combinations of commonly used and last-resort antibiotics.

 

Of 33 antibiotics in development targeting priority pathogens, just nine belong to five new antibiotic classes. Image: Public Domain Pictures

‘The end of the antibiotic era isn’t on the horizon just yet,’ Brown says. ‘But we can see it wouldn’t take much to get that way.’

Failure to tackle antibiotic-resistant superbugs could result in 10m deaths a year by 2050, according to the UK government-commissioned Review on Antimicrobial Resistance. The UN and G20 have both made political commitments to combat the problem. Nevertheless, time is running out.

‘This is an urgent and rapidly rising global health problem,’ says Ghada Zoubiane, science lead for the Wellcome Trusts’ drug-resistant infections team. ‘We need greater investment in developing new ways to treat and protect people from these deadly infections and we need better understanding of how resistance spreads.’

What causes antibiotic resistance? Video: TED-Ed

Despite calls for increased R&D, no new classes of antibiotics have been approved since the early 1980s, apart from the approval of linezolid in 2000, and the last new class to treat Gram-negative bacteria was discovered in 1962, Zoubiane says.

Big pharma withdrew en masse from the antibiotic space in the 1990s, due to the low returns on the high level of investment required in antibiotic R&D. Recognising the urgency of the problem, however, in January 2016 more than 90 pharma and biotech companies committed to enhancing antibiotic discovery.

The move has been accompanied by more research into understanding resistance mechanisms, as well as a shift to more outside-of-the-box thinking about alternative treatments.

 

In 2016, over $500m was invested into research into antibiotic resistance. Image: PxHere

In February 2017, the World Health Organization (WHO) published its list of 12 antibiotic-resistant ‘priority pathogens’ that pose the greatest threat to human health. Most notable are the Gram-negative bacteria, which possess an additional outer cell membrane and are harder to treat with antibiotics than Gram-positive bacteria.

‘These bacteria have been assessed as the most critical priority for antibiotic R&D, as strains are emerging worldwide that cannot be treated with any of the antibiotics currently on the market,’ WHO says.

Despite the increased commitment to R&D, however, a WHO report in September 2017 lamented the ‘serious lack of new antibiotics under development’. Among the 33 new chemical entity antibiotics in development targeting priority pathogens, just nine belong to five new antibiotic classes.

There are 16 products, both antibiotics and biologics, with activity against one or more Gram-positive priority pathogens – although mostly targeting methicillin-resistant Staphylococcus aureus (MRSA) – including two new antibiotic classes.

Meanwhile, ‘the situation is worse for Gram-negative bacterial infections’, says WHO. Of ten products in Phase 1 trials, ‘almost all the agents are modifications of existing antibiotic classes […] active only against specific pathogens or a limited subset of resistant strains’.

The 2016 Lister Memorial Lecture: Dame Sally Davies on Global antiiotic resistance. Video: SCI

WHO warns that ‘more investment is needed in basic science, drug discovery and clinical development, especially for the critical priority Gram-negative carbapenem-resistant pathogens P. aeruginosa, A. baumannii, and Enterobacteriaceae.’

‘We need to find a strategy not to overcome resistance, but to be able to live with and manage it,’ Brown reflects. ‘I’m more optimistic than some. It’s important to remember that before antibiotics were discovered, the human race didn’t die out.’

Antimicrobial drug discovery

 

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A new drug developed by Eli Lilly to combat the symptoms of psoriatic arthritis (PsA) – including severe joint pain and swelling – has been approved for market by the European Commission.

Ixekizumab, or Taltz®, can be used to treat patients with PsA who have not responded to, or are intolerant to, traditional anti-rheumatic drug therapies, such as methotrexate, which act to treat the underlying cause of arthritis to slow disease progression, rather than the symptoms.

PsA is caused by a fault in a person’s immune system, when the body sends out signals for inflammation even when damage has not occurred., causing swollen, stiff, and painful joints. It is a chronic and progressive disease with no known cure.

Vaccines are much debated these days, but before starting a discussion about them, let’s see how a vaccine is defined.

The World Health Organisation defines a vaccine as: 

‘a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body’s immune system to recognize the agent as foreign, destroy it, and “remember” it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.’

We put in our bodies something that looks like or has a tiny part of the ‘microbe’ that produces the disease so that our body can produce the right agents to fight it in case we actually contract the real illness.

A vaccine is comprised of an active ingredient and other added ingredients. Like any other drug, the active ingredient is the key component that triggers the immune response. Beside this, the added ingredients have different roles, such as improving the immune response, or acting as a preservative, stabiliser, or suspending fluid.

These added ingredients are the ones that are sometimes contested due to their toxicity. But when speaking about toxicity, there is a very important point to make. Everything is toxic.

It all comes down to the dose you eat, drink, or otherwise insert into your body. An important indicator of toxicity is LD50 (lethal dose 50), which is the dose at which 50% of individuals die. Sodium chloride, also known as table salt, has a LD50 of 12,400mg/kg (868g of salt for a 70kg individual) for humans. The lower the LD50 indicator is, the more toxic a compound is.

Originally posted by gifsme

Table salt can also be toxic. 

Aluminium salts are used in many vaccines as adjuvants. This means that they help by stimulating the immune response and by a slow release of the active ingredient.

The most used salts are aluminium hydroxide, aluminium phosphate and potassium aluminium sulphate. Data about these compounds are freely accessible by searching for their material safety data sheets (MSDS) on the big chemical suppliers’ websites. The 11th section of an MSDS file is the toxicological information section, which contains the LD50 value, carcinogenicity information, and others.

 

Section 11 of the aluminium phosphate MSDS Sigma-Aldrich

None of the salts above are reported as carcinogenic, and the LD50 of aluminium phosphate is more than 5,000mg/kg for mice. The total quantity of the aluminium in a vaccine is less 1mg (0.001g), which is a very low quantity. In the normal European diet the amount of aluminium we intake from food varies between 3–10mg a day.

Vaccine composition lists also include compounds and products used in the manufacturing process – even though at the end of manufacture they are present only in trace amounts, if at all.

One of the chemicals on this list that scares people is formaldehyde, which is indeed carcinogenic with and LD50 of 42mg/kg for mice. Nevertheless, the quantity present in a vaccine dose is less 0.1 mg. One 200g pear contains 12mg of formaldehyde. We should always remember ‘the dose makes the poison’, as compound interest illustrates below.

 

The does makes the poison – ‘toxic’ chemicals in food. Compound Interest

Vaccination is a personal decision. Nevertheless, it should be based on information from multiple verified sources. Easily accessible and clear information can be found on the Vaccine Knowledge Project website designed by the Vaccine Research Group from the University of Oxford.

The US is in the midst of a healthcare epidemic. Tens of thousands of people are dying each year from opioid drugs, including overdoses from prescription painkillers such as OxiContin (oxycodone) and the illicit street drug heroin, and each year the numbers rise.

The opioid epidemic is currently killing almost twice as many people as shootings or motor vehicle accidents, with overdoses quadrupling since 1999. According to Gary Franklin, medical director of the Washington State Department of Labour and Industries and a professor of health at the University of Washington, the opioid epidemic is ‘the worst man-made epidemic in modern medical history in the US’.

 

Montgomery, Ohio, is at the centre of the epidemic, with the most opioid-related deaths per capita this year. Image: Wikimedia Commons

Incredibly, an influx of synthetic opioids is making the problem worse. Fentanyl, a licensed drug to treat severe pain, is increasingly turning up on the street as illicit fentanyl, often mixed with heroin. According to the NCHS, fentanyl and synthetic opioids are blamed for 20,145 of the 64,070 overdose deaths in 2016. Heroin contributed to 15,446 deaths, while prescription opioids caused 14,427.

Potent opioid

Fentanyl (C22H28N20), a lipophilic phenylpiperidine opioid agonist, is generally formulated as a transdermal patch, lollipop and dissolving tablet. Like the opioids derived from opium poppies, such as morphine, fentanyl binds to opioid receptors in the brain and other organs of the body, specifically the mu-receptor.

 

Heroin and other opioids come from the opium poppy.  Image: Max Pixel

Such binding mimics the effects of endogenous opiates (endorphins), creating an analgesic effect, as well as a sense of well-being when the chemical binds to receptors in the rewards region in the brain. Drowsiness and respiratory depression are other effects, which can lead to death from an overdose.

Rise of illicit fentanyl

The opioid epidemic can be traced back to the 1990s when pharmaceutical companies began producing a new range of opioid painkillers, including oxycodone, touting them as less prone to abuse. In addition, prescribing rules were relaxed, while advocates championed the right to freedom from pain. Soon, opioids were being prescribed at alarming rates and increasing numbers of patients were becoming hooked.

Why is there an opioid crisis? Video: SciShow

Franklin, who was the first person to report in 2006 on the growing death rate from prescribed opioids, says: ‘OxyContin is only a few atoms different to heroin – I call it pharmaceutical heroin.’

A crackdown on prescribing was inevitable. But then, with a shortage of prescription opioids, addicts turned to illicit – and cheaper – heroin. According to Franklin, 60% of heroin users became addicted via a prescribed opioid. ‘You don’t have to take these drugs for very long before it’s very hard to get off,’ he says: ‘Just days to weeks.’ Heroin use soared and with it increased tolerance, leading users to seek out more potent highs. By 2013, there were almost 2m Americans struggling with an opioid-use disorder.

Drugs to fight drugs

 

President Trump declared the opioid crisis a public health emergency in October. Image: Pixabay 

Attention is finally being given to the epidemic. US president Donald Trump recently declared a public health emergency, although no new funds will be assigned to deal with the crisis.

There is particular interest around research into a vaccine against fentanyl. Developed by Kim Janda at The Scripps Research Institute, California, US, the vaccine, which has only been tested in rodents, can protect against six different fentanyl analogues, even at lethal doses. ‘What we see with the epidemic, is the need to find alternatives that can work in conjunction with what is used right now,’ he says.

This vaccine could treat heroin addiction. Video: Seeker

The vaccine works by taking advantage of the body’s immune system to block fentanyl from reaching the brain. Its magic ingredient is a molecule that mimics fentanyl’s core structure, meaning the vaccine trains the immune system to recognise the drug and produce antibodies in its presence. These antibodies bind to fentanyl when someone takes the drug, which stops it from reaching the brain and creating the ‘high’.

Platinum is one of the most valuable metals in the world. Precious and pretty, it’s probably best known for jewelry – and that is almost certainly its oldest use. But its value has become far greater than its decorative ability; today, platinum powers the world. From agriculture to the oil markets, energy to healthcare, we use platinum far more than we realise.

1. Keep the car running

 

Platinum is needed to make fuel for transport. Image: Pixabay

Platinum catalysts are crucial in the process that converts naphtha into petrol, diesel, and jet-engine fuel, which are all vital to the global economy. The emissions from those petroleum fuels, however, can be toxic, and platinum is also crucial in the worldwide push to reduce them through automotive catalytic converters. In fact, 2% of global platinum use in 2016 was in converting petroleum and 41% went into reducing emissions – a circle of platinum use that’s more impressive than a ring.

2. Feed the world

 

Nitric acid is a by-product of platinum which is used in fertilisers. Image: Pixabay

Another vital global sector that makes use of platinum catalysts is agriculture. Without synthetic fertilisers, we would not be able to produce nearly as much food as we need. Nitric acid is essential for producing those fertilisers and platinum is essential for producing nitric acid. Since 90% of the gauzes required for nitric acid are platinum, we may need to use more of it as we try to meet the global food challenge.

3. Good for your health

 

A pacemaker. Image: Steven Fruitsmaak@Wikimedia Commons 

Platinum is extremely hard wearing, non-corrosive, and highly biocompatible, making it an excellent material to protect medical implants from acid corrosion in the human body. It is commonly used in pacemakers and stents. It is also used in chemotherapy, where platinum-based chemotherapeutic agents are used to treat up to 50% of cancer patients.

4. The fuel is clean

In addition to powering the cars of the present and reducing their environmental impact, platinum might well be crucial to the future of transport in the form of fuel cells. Platinum catalysts convert hydrogen and oxygen into clean energy, with water the only by-product.

5. Rags to riches

 

The Spaniards invaded the Inca Empire, South America, in 1532. Painted by Juan B Lepiani. Image: MALI@Wikimedia Commons

Amazingly, despite all this, platinum was once considered worthless - at least in Europe. In fact, it was considered a nuisance by the Spanish when they first discovered it in South America - as a corruption in the alluvial deposits they were earnestly mining and they would quite literally throw it away. It wasn’t until the 1780s that the Spanish realised it might have some value.

Because platinum is essential to so many aspects of our economy, there are concerns about supply meeting demand – particularly as nearly 80% is currently mined in South Africa, which has seen its mining industry repeatedly crippled by strikes in recent years. 

 

Two Rivers platinum mine, South Africa. Image: Wikimedia Commons

Some believe the solution to the issue of supply is space mining, arguing the metal could be found in asteroids.

Others, such as researchers at MIT, are working to create synthetic platinum, using more commonly found materials. Neither approach is guaranteed to work but, given our increasing dependence on this precious metal, we could be more reliant on their success than we realise.

Around 10 million medical devices are implanted each year into patients, while one-third of patients suffer some complication as a result. Now, researchers in Switzerland have developed a way to protect implants by dressing them in a surgical membrane of cellulose hydrogel to make them more biocompatible with patients’ own tissues and body fluids.  

‘It is more than 60 years since the first medical implant was implanted in humans and no matter how hard we have tried to imitate nature, the body recognises the implant as foreign and tends to initiate a foreign body reaction, which tries to isolate and kill the implant,’ says Simone Bottan at, who leads ETH Zurich spin-off company Hylomorph.

 

Hylomorph is a spin-off company of ETH Zurich, Switzerland. Image: ETH-Bibliothek@Wikimedia Commons

Up to one-fifth of all implanted patients require corrective intervention or implant replacement due toan immune response that wraps the implant in connective tissue (fibrosis), which is also linked with infections and can cause patients pain. Revision surgeries are costly and require lengthy recovery times.

The new membrane is made by growing bacteria in a bioreactor on micro-engineered silicone surfaces, pitted with a hexagonal arrangement of microwells. When imprinted onto the membrane, the microwells impede the formation of layers of fibroblasts and other cells involved in fibrosis.

 

25,000 people in the UK have a pacemaker fitted each year. Image: Science Photo Library

The researchers ‘tuned’ the bacteria, Acetobacter xylinum, to produce ca 800 micron-thick membranes of cellulose nanofibrils that surgeons can wrap snuggly around implants. The cellulose membranes led to an 80% reduction of fibrotic tissue thickness in a pig model after six weeks, according to a study currently in press. Results after three and 12 months should be released in January 2018.

It is hoped the technology will receive its first product market authorisation by 2020. First-in-man trials will focus on pacemakers and defibrillators and will be followed by breast reconstruction implants. The strategy will be to coat the implant with a soft cellulose hydrogel, consisting of 98% water and 2% cellulose fibres.  

The membrane will improve the biocompatibility of implants. Video: Wyss Zurich

‘Fibrosis of implantables is a major medical problem,’ notes biomolecular engineer Joshua Doloff at Massachusetts Institute of Technology, adding that many coating technologies are under development.

‘[The claim] that no revision surgery due to fibrosis will be needed is quite a strong claim to make,’ says Doloff, who would also like to see data on the coating’s robustness and longevity.

The silicone topography is designed using standard microfabrication techniques used in the electronics industry, assisted by IBM Research Labs.  

 

Delegates at this year’s Young Chemist in Industry conference. Image: SCI

Every year, SCI’s Young Chemist’s Panel organise their Young Chemist in Industry event, where early career industrial chemists meet to showcase their research and network with their academics counterparts and other companies. 

This year, the conference was held at AstraZeneca’s Macclesfield base. Exhibitors are also judged, with the winner receiving a £150 Amazon voucher.

 

Julien Vantourout. Image: SCI

This year’s Young Chemist in Industry award went to Julian Vantourout, a final-year industrial PhD student at GSK and the University of Strathclyde.

His presentation focused on the limitations of the Chan-Lam amination of aryl boronic acid used in medicinal and process chemistry.

 

Tim O'Riordan and Ellen Gallimore. Image: SCI

Two runners-up received a £50 Amazon voucher each; Tim O’Riordan and Ellen Gallimore. 

Tim O’Riordan is a Principal Research Chemist in Syngenta’s crop protection department. he won the runner-up prize this year for his work in the synthesis and evaluation of new herbicides.

Ellen Gallimore is currently finishing her DPhil at Oxford University and works for UCB in their medicinal chemistry department. She received the runner-up prize for her exhibit explaining the biocatalytical potential of enzymes on small molecule drug discovery.

 

Image: Fluorochem Ltd

Fluorochem Ltd were at the event promoting their business to delegates. They supply intermediates used in R&D to pharmaceutical companies.

 

Image: Manchester Organics

Manchester Organics work in fluorination and high pressure chemistry.

 

Image: Radleys

Radleys were on hand to tell delegates about their sustainable chemistry equipment.

It has been a year since Prime Minister Theresa May announced the launch of the Industrial Strategy Challenge Fund at CBI’s annual conference. At the time, May said the fund would ‘help to address Britain’s historic weakness on commercialisation and turning our world-leading research into long-term success’.

Since then, Innovate UK has worked closely with the government and research councils to identify the great innovation challenges the UK faces.

‘Innovate UK have been in this right from the very beginning,’ said Ruth McKernan, Chief Executive of Innovate UK, speaking at Innovate 2017. McKernan explained that the organisation has held several engagement events to find out what ‘industry and researchers see as the challenges of the future and where economic growth can be developed in the UK’.

The first three challenges sponsored by the Industrial Strategy Challenge Fund were announced in April this year: The Faraday challenge, medicines manufacturing, and robotics and autonomous systems.

Andrew Tyrer, Interim Director of Robotics and Autonomous Systems is now responsible for the £69m investment into research on AI in extreme conditions.

Research projects in this cohort include robotics in deep mining, space exploration, and off-shore energy. ‘One of the challenges is that you cannot put people in these environments,’ he said.

 

Space is just one of the dangerous environments being researched in robotics projects. Image: NASA

However, the UK does not currently have the research capacity to access the global market, Tyrer explained. For example, he said ‘the nuclear decommissioning market in five years will be at £150bn a year in Europe alone’ – a market the UK is currently struggling to make an impact.

‘The programme is about taking academic and business excellence, linking those value chains together, and building those industries,’ Tyrer said.

On the other end of the spectrum, is the Faraday Challenge – a ‘commitment’ to research into the battery development of driverless cars and an area of research the UK has already seen success in – headed by Jacqui Murray and Kathryn Magnay.

 

The UK have pledged to have all petrol and diesel vehicles off roads by 2040. Image: Wikimedia Commons

‘Automotive has been a real success story in the UK in the last 10 years,’ said Murray, with the UK reaching ‘world-class’ in productivity levels.

However, there are ways the UK needs to improve, said Magnay. ‘In the UK we have a huge gap between the research that we do and how you scale that up in the manufacturing process,’ she said.

This is the inspiration for the upcoming £65m Faraday Battery Institute, which will serve as a hub for universities, as well as other academic institutions and industry partners, to further their science. Magnay said that Innovate UK wants to ‘provide a facility that companies and researchers can go to and take their ideas to trial them at scale’.

Will smart energy solutions be the next challenge?

Further challenges under the Industrial Strategy Challenge Fund are currently unknown, although there are rumours of an early 2018 announcement. Which challenge will be next?

Some could argue the greatest threat to life as we know it is the slow, invisible war being fought against antibiotic resistant bacteria. The accidental discovery of penicillin by Fleming in the late 1920s revolutionised modern medicine, beginning with their use in the Second World War.

Over-prescription of these wonder drugs has allowed bacteria, which multiply exponentially, the ability to pick up on deadly cues in their environment at a phenomenal rate. They’re adapting their defence mechanisms so they’re less susceptible to attack. In theory, with an endless supply of different drugs, this would be no big deal.

 

Alexander Fleming, who discovered penicillin. Image: Wikimedia Commons

Unfortunately, the drug pipeline seems to have run dry, whilst the incidence of resistance continues to climb. For the gnarliest of infections, there’s a list of ‘drugs of last resort’, but resistance even to some of these has recently been observed. A report published by the World Health Organisation echoes these warnings – of the 51 new drugs in clinical development, almost 85% can be considered an ‘upgraded’ version of ones on the market right now. These drugs are a band aid on a snowballing problem.

Are viruses the answer?

Bacteriophages, or phages for short, are viruses that infect only bacteria, wreaking havoc by hijacking cellular machinery for their growth and development.

 

A bacteriophage. Image: Vimeo

Phages can find themselves in one of two different life cycles: virulent and temperate. The first involves constant viral replication, killing bacteria by turning them inside out (a process known as lysis). The second life cycle allows the phage in question to hitch a ride in the cell it infects, integrating its genetic material into the host’s and in doing so, propagating without causing immediate destruction. It’s the former that is of value in phage therapy.

Long before Fleming’s discovery, phages were employed successfully to treat bacterial infections. In areas of Eastern Europe, phages have been in continuous clinical use since the early part of the 20th century. 

Why did their use not take off like that of penicillin’s in the West? ‘Bad science’ that couldn’t be validated in the early days proved to be disheartening, and phages were pushed to the wayside. Renewed interest in the field has come about due to an improvement in our understanding of molecular genetics and cell biology.

Originally posted by futuristech-info

Phages are highly specific and, unlike antibiotics, they don’t tamper with the colonies of bacteria that line our airways and make up a healthy gut microbiome. As they exploit an entirely different mode of action, phages can be used as a treatment against multiple drug-resistant bacteria. 

Repeated dosing may not even be necessary – following initial treatment and replication of the phage within infected cells, cell lysis releases ever more phages. Once the infection is cleared, they’re excreted from the body with other waste products.

What is holding it back?

A number of key issues must be ironed out if phage therapy is to be adopted to fight infection as antibiotics have. High phage specificity means different phage concoctions might be needed to treat the same illness in two different people. Vast libraries must be created, updated and maintained. Internationally, who will be responsible for maintenance, and will there be implications for access?  

Scientists are looking at new ways to tackle antibiotic resistance. Video: TEDx Talks

Despite proving a promising avenue for (re)exploration, under-investment in the field has hindered progress. Bacteriophage products prove hard to patent, impacting the willingness of pharmaceutical companies investing capital. AmpliPhi Biosciences, a San Diego-based biotech company that focuses on the ‘development and commercialization of novel bacteriophage-based antibacterial therapeutic,’ was granted a number of patents in 2016, showing it is possible. This holds some promise – viruses might not save us yet, but they could be well on their way to.

What is paralysis? Video: Doctors’ Circle

Patients suffering from paralysis can at last look forward to a time when their condition is cured, and they can walk, run or move their damaged limbs again, as recent advancements show the possibility of reversal.    

‘The environment has never been better for exploring ways to restore neurological function, including paralysis – in fact, there has been a dramatic escalation of the entire research spectrum aimed at functional neurorestoration,’ says Charles Liu, Director of the University of Southern California Neurorestoration Center.

Paralysis comes in many forms: the paralysis of one limb (monoplegia), one side of the body (hemiplegia), below the waist (paraplegia), and all four limbs below the neck (tetraplegia, or also referred to as quadriplegia).

 

There are many classifications of paralysis. It can be localised or generalised, and can affect most areas of the body. Image: Pixabay

In an able-bodied person, the brain sends a signal as an electrical impulse, known as an action potential, down the spinal cord to the peripheral nerves, which instruct the muscles to contract and move, whereupon sensors in the muscles and skin send signals back to the brain.

In most paralysis cases, the condition occurs as a result of damage to nerves rather than an injury to the affected area. Strokes are the most common cause of paralysis, followed by spinal cord injuries. Multiple sclerosis, cerebral palsy, polio, head injuries and several other rare diseases can also cause paralysis.  

Regenerating neurons

‘Long term, we hope to cure paralysis and make the injured walk,’ explains William Sikkema, a graduate student at Rice University, Houston. The challenge is not only to repair cells but to restore connectivity, too. In collaboration with researchers at Konkuk University in South Korea, the team has already made a paralysed rat walk again.

The addition of graphene nanoribbons restored motor and sensory neuronal signals across the previous nerve gap after 24 hours, with almost perfect motor control recovery after a period of healing. ‘Two weeks later, the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls,’ the team reported.

‘After a neuron is cut, it doesn’t know where to grow. So, it either doesn’t grow, or grows in the wrong direction,’ says Sikkema. ‘Our graphene nanoribbons act as a scaffolding track, and it tells the neurons where to grow.’

 

Rats are a common animal model in paralysis studies, as they share similar structure and functions with humans. Image: Pexels

Spinal cord stimulation

Electrical stimulation of the spinal cord could also provide a big breakthrough, says Chet Moritz, Co-Director of the Center for Sensorimotor Neural Engineering at the University of Washington, US.

‘We’re seeing some really impressive results with spinal cord stimulation where people with complete paralysis, who have been unable to function, have regained control of their limbs. We didn’t expect this. It’s the most exciting thing we’ve seen in the last 20 years,’ he says.

Last year, a team led by Grégoire Courtine at the Swiss Federal Institute of Technology inserted an implant in the brains of paralysed monkeys and another over the spinal cord below the injury. The brain-spine interface worked by capturing leg-moving brain signals, decoded by a computer and sent – bypassing the damaged region – to the second implant, which delivered the signals as electrical impulses to the nerves, causing the leg to move.

Grégoire Courtine talks about his pioneering work on paralysis using electrical stimulation. Video: TED

Within six days, the monkeys had regained the use of their lower limbs and improved even more over time. The success of the experiment has led Courtine to launch a human trial of a spinal implant system.

We may be a long way still from restoring full function, as prior to paralysis, but Moritz is optimistic. Even a modest change, such as the movement of a single finger, can have a dramatic effect on quality of life and independence. ‘In five years, we’ve had dramatic improvement in function,’ he says. ‘It’s an exciting trajectory with tremendous potential.’  

What is paralysis? Video: Doctors’ Circle

Patients suffering from paralysis can at last look forward to a time when their condition is cured, and they can walk, run or move their damaged limbs again, as recent advancements show the possibility of reversal.    

‘The environment has never been better for exploring ways to restore neurological function, including paralysis – in fact, there has been a dramatic escalation of the entire research spectrum aimed at functional neurorestoration,’ says Charles Liu, Director of the University of Southern California Neurorestoration Center.

Paralysis comes in many forms: the paralysis of one limb (monoplegia), one side of the body (hemiplegia), below the waist (paraplegia), and all four limbs below the neck (tetraplegia, or also referred to as quadriplegia).

There are many classifications of paralysis. It can be localised or generalised, and can affect most areas of the body. Image: Pixabay

In an able-bodied person, the brain sends a signal as an electrical impulse, known as an action potential, down the spinal cord to the peripheral nerves, which instruct the muscles to contract and move, whereupon sensors in the muscles and skin send signals back to the brain.

In most paralysis cases, the condition occurs as a result of damage to nerves rather than an injury to the affected area. Strokes are the most common cause of paralysis, followed by spinal cord injuries. Multiple sclerosis, cerebral palsy, polio, head injuries and several other rare diseases can also cause paralysis.  

Originally posted by palerlotus

---

Regenerating neurons

‘Long term, we hope to cure paralysis and make the injured walk,’ explains William Sikkema, a graduate student at Rice University, Houston. The challenge is not only to repair cells but to restore connectivity, too. In collaboration with researchers at Konkuk University in South Korea, the team has already made a paralysed rat walk again.

The addition of graphene nanoribbons restored motor and sensory neuronal signals across the previous nerve gap after 24 hours, with almost perfect motor control recovery after a period of healing. ‘Two weeks later, the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls,’ the team reported.

‘After a neuron is cut, it doesn’t know where to grow. So, it either doesn’t grow, or grows in the wrong direction,’ says Sikkema. ‘Our graphene nanoribbons act as a scaffolding track, and it tells the neurons where to grow.’

Rats are a common animal model in paralysis studies, as they share similar structure and functions with humans. Image: Pexels

---

Spinal cord stimulation

Electrical stimulation of the spinal cord could also provide a big breakthrough, says Chet Moritz, Co-Director of the Center for Sensorimotor Neural Engineering at the University of Washington, US.

‘We’re seeing some really impressive results with spinal cord stimulation where people with complete paralysis, who have been unable to function, have regained control of their limbs. We didn’t expect this. It’s the most exciting thing we’ve seen in the last 20 years,’ he says.

Last year, a team led by Grégoire Courtine at the Swiss Federal Institute of Technology inserted an implant in the brains of paralysed monkeys and another over the spinal cord below the injury. The brain-spine interface worked by capturing leg-moving brain signals, decoded by a computer and sent – bypassing the damaged region – to the second implant, which delivered the signals as electrical impulses to the nerves, causing the leg to move.

Grégoire Courtine talks about his pioneering work on paralysis using electrical stimulation. Video: TED

Within six days, the monkeys had regained the use of their lower limbs and improved even more over time. The success of the experiment has led Courtine to launch a human trial of a spinal implant system.

We may be a long way still from restoring full function, as prior to paralysis, but Moritz is optimistic. Even a modest change, such as the movement of a single finger, can have a dramatic effect on quality of life and independence. ‘In five years, we’ve had dramatic improvement in function,’ he says. ‘It’s an exciting trajectory with tremendous potential.’  

What is paralysis? Video: Doctors’ Circle

Patients suffering from paralysis can at last look forward to a time when their condition is cured, and they can walk, run or move their damaged limbs again, as recent advancements show the possibility of reversal.    

‘The environment has never been better for exploring ways to restore neurological function, including paralysis – in fact, there has been a dramatic escalation of the entire research spectrum aimed at functional neurorestoration,’ says Charles Liu, Director of the University of Southern California Neurorestoration Center.

Paralysis comes in many forms: the paralysis of one limb (monoplegia), one side of the body (hemiplegia), below the waist (paraplegia), and all four limbs below the neck (tetraplegia, or also referred to as quadriplegia).

There are many classifications of paralysis. It can be localised or generalised, and can affect most areas of the body. Image: Pixabay

In an able-bodied person, the brain sends a signal as an electrical impulse, known as an action potential, down the spinal cord to the peripheral nerves, which instruct the muscles to contract and move, whereupon sensors in the muscles and skin send signals back to the brain.

In most paralysis cases, the condition occurs as a result of damage to nerves rather than an injury to the affected area. Strokes are the most common cause of paralysis, followed by spinal cord injuries. Multiple sclerosis, cerebral palsy, polio, head injuries and several other rare diseases can also cause paralysis.  

Originally posted by palerlotus

---

Regenerating neurons

‘Long term, we hope to cure paralysis and make the injured walk,’ explains William Sikkema, a graduate student at Rice University, Houston. The challenge is not only to repair cells but to restore connectivity, too. In collaboration with researchers at Konkuk University in South Korea, the team has already made a paralysed rat walk again.

The addition of graphene nanoribbons restored motor and sensory neuronal signals across the previous nerve gap after 24 hours, with almost perfect motor control recovery after a period of healing. ‘Two weeks later, the rat could walk without losing balance, stand up on his hind limbs and use his forelimbs to feed himself with pellets. No recovery was observed in controls,’ the team reported.

‘After a neuron is cut, it doesn’t know where to grow. So, it either doesn’t grow, or grows in the wrong direction,’ says Sikkema. ‘Our graphene nanoribbons act as a scaffolding track, and it tells the neurons where to grow.’

Rats are a common animal model in paralysis studies, as they share similar structure and functions with humans. Image: Pexels

---

Spinal cord stimulation

Electrical stimulation of the spinal cord could also provide a big breakthrough, says Chet Moritz, Co-Director of the Center for Sensorimotor Neural Engineering at the University of Washington, US.

‘We’re seeing some really impressive results with spinal cord stimulation where people with complete paralysis, who have been unable to function, have regained control of their limbs. We didn’t expect this. It’s the most exciting thing we’ve seen in the last 20 years,’ he says.

Last year, a team led by Grégoire Courtine at the Swiss Federal Institute of Technology inserted an implant in the brains of paralysed monkeys and another over the spinal cord below the injury. The brain-spine interface worked by capturing leg-moving brain signals, decoded by a computer and sent – bypassing the damaged region – to the second implant, which delivered the signals as electrical impulses to the nerves, causing the leg to move.

Grégoire Courtine talks about his pioneering work on paralysis using electrical stimulation. Video: TED

Within six days, the monkeys had regained the use of their lower limbs and improved even more over time. The success of the experiment has led Courtine to launch a human trial of a spinal implant system.

We may be a long way still from restoring full function, as prior to paralysis, but Moritz is optimistic. Even a modest change, such as the movement of a single finger, can have a dramatic effect on quality of life and independence. ‘In five years, we’ve had dramatic improvement in function,’ he says. ‘It’s an exciting trajectory with tremendous potential.’  

In recent years, novel innovation in healthcare and pharmaceuticals have hit the headlines with increasing regularity. Each story promises a better quality of life for patients and a product that will ‘revolutionise’ healthcare as we know it. 

However, many of these innovations fail to materialise due to the complexity of the system. Problems with regulation, intellectual property agreements, and manufacturing are just some of the many issues that industry faces when integrating a new product into hospitals and treatment centres.

 

Stephen Dorrell. Image: NHS Confederation@Flickr

So, do we need rethink our expectations of innovation? Speaking at New Scientist Live in September, Stephen Dorrell, Chair of NHS Confederation and a former Health Secretary, said that as an innate characteristic of humans, innovation will not stop. However, we should be more concerned about the difficulty of making good innovation available everywhere and rethinking what we consider the most efficient way of treating patients, he said.

As the most common type of dementia – affecting one in six over the age of 80 – Alzheimer’s disease needs good innovation. With no known cure, current efforts rely heavily on having a care plan once symptoms appear and medications can only slightly improve symptoms for a time as well as slow down the progression of the disease.

Progress in pharmaceuticals 

The Alzheimer’s research community are well versed in the known causes of the disease, with amyloid plaques and tau tangles the most widely accepted causes of the neurodegeneration that leads to Alzheimer’s. As a result, the majority of research and investment in the field is centred around this theory.

Neuro-Bio is a biotechnology start-up that is taking a different approach to making medicines for Alzheimer’s patients. The company is focused on a ‘previously unidentified mechanism’ of the disease that is linked to the development stages of the brain and cell death, and is working on new drug candidates that can stop the peptide involved in this mechanism from functioning improperly in adults.

After a series of setbacks in Alzheimer’s drug development, Prof Margaret Esiri, a neuropathologist at the Nuffield Department of Clinical Sciences, Oxford, said: ‘Neuro-Bio’s approach to the problem of Alzheimer’s disease is novel and scientifically well-founded. It is a good example of the new thinking that is urgently needed in this field’.

Timing it right 

However, with an uncertainty for future success in Alzheimer’s pharmaceuticals, researchers interested in the genetic make-up of neurodegenerative diseases are focusing on how early diagnosis can be beneficial to patients.

 

Alzheimer’s can cause a significant loss of brain matter (right) compared to a healthy brain (left). Image: National Institutes of Health

According to UCL geneticist John Hardy, a loss in brain matter and amyloid build-up begins 15 to 20 years before symptoms start to appear, highlighting the need for preventative measures. This need is not consistent with what is currently available to patients in the UK however, as to qualify for a clinical trial, patients must be in the advanced stages of Alzheimer’s – often exhibiting severe symptoms that can, quite drastically, negatively affect quality of life for the individual.

Scientists at Case Western Reserve University, Ohio, US, may have solved this issue of early diagnosis after developing a machine learning program that outperforms other methods for diagnosing Alzheimer’s disease. The program integrates known disease indicators and symptoms to predict the likelihood of Alzheimer’s onset. Multiple stage comparisons, which includes associated symptoms that are not always present in Alzheimer’s, allow the program to make a more accurate prediction of who is most vulnerable.

Development of such programs could help initiatives such as the 100,000 Genomes Project which aims to provide the NHS with a new genomic medicine service that can offer better diagnosis and more personalised treatments.  

 

Baroness Susan Greenfield. Image: National Assembly for Wales

Interested in Alzheimer’s disease?

SCI is running a Public Evening Lecture in London on Wednesday 28 February – The 21st Century mind: Blowing it, expanding it, losing it. The talk will be given by Baroness Susan Greenfield, neuroscientist and CEO of Neuro-bio. It is free to attend, but spaces are limited. Don’t miss out – booking opening soon.