Prestigious £1.7m Professional medical Study Council Fellowship for clinical trials scientist
A senior scientist with the University of Aberdeen has been awarded a considerable fellowship from the Health-related Exploration Council (MRC) to investigate how to maximise the prospective for behavioural science to strengthen how scientific trials are operate.
Dr Katie Gillies, Director of the Health and fitness Treatment Evaluation Programme, at the University’s Wellbeing Companies Investigate Device (HSRU), has been awarded a £1.7m Senior Non-Scientific Fellowship (SNCF) which will guidance three scientists and a PhD student around a interval of five several years.
The HSRU has a national remit to study the finest techniques to give wellbeing treatment and to prepare individuals doing work in health expert services in research approaches.
Scientific trials are the primary scientific way to examine treatment plans in purchase to demonstrate which is better. A ‘treatment‘ could signify a drug, or an operation, a system (e.g. a catheter) or a physical or psychological remedy. Millions of individuals get element in medical trials globally just about every 12 months – more than 7.4 million past year alone. This sizeable contribution in range of members needed is matched by the sizeable contribution in terms of price tag.
Dr Gillies describes: “Trials are expensive. The Uk expended pretty much £100 million on trials all through 2019-2020 just as a result of the National Institute for Wellness Investigate Wellness Technological know-how Assessment programme.
“This proposed programme of analysis aims to create techniques to increase the perform of clinical trials and will exclusively glimpse at how people’s behaviours, like what they do and how, affects their success.
“The investigation has the probable to crank out a move-adjust in the way trial groups produce scientific trials by addressing who desires to do what differently to whom, when and how. The promise of this analysis is the major enhancements to trials from making use of far better methods to structure and carry out better trials for the millions of clients who take part each calendar year.
“The receipt of this fellowship is important simply because it gives source to make it possible for me and my crew to focus on researching no matter if and how behavioural science can be made use of to maximise the delivery of scientific trials to improve patient gain. I am delighted to obtain this fellowship and hope that it highlights the great importance of trials techniques analysis as a precedence for long run funding.”
Professor Marion Campbell, Vice-Principal Exploration at the University of Aberdeen, added:
“MRC Senior Non-Scientific Fellowships are awarded to outstanding people today who are top truly progressive analysis. My congratulations go to Dr Gillies whose accomplishment is testomony to the toughness of academic expertise that exists here at the University.”
The use of experimental therapies based on bacteria-killing viruses needs to be rapidly scaled up in the NHS to combat the worsening threat of antibiotic resistance, one of the UK’s leading scientists has said.
Prof Martha Clokie, who has pioneered research into bacteriophages, or phages, at the University of Leicester, said the approach was helping a growing number of patients in compassionate use cases, and could become a routine treatment in future for conditions such as chronic UTIs and diabetic foot ulcers.
Clokie will be the director of the UK’s first phage library, due to open at Leicester next month, which she says will help fast-track the use of phages in the NHS and pave the way for the large clinical trials required for phages to become licensed treatments.
“The risk from antibiotic resistance is dire and getting worse … I find it really shocking,” Clokie said. “Unless we have clinical trials, phages won’t become mainstream as a medicine, and that’s where we’re aiming.”
Phages work by infecting bacteria cells and killing them, but they are very specific in which infections they can target. They have been used successfully in a growing number of one-off cases, including a British teenager who was dying from an intractable lung infection and was treated at Great Ormond Street in 2019.
Q&A
What are bacteriophages?
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Bacteriophages, or phages, are incredibly small viruses, just a few nanometres across. They are normally harmless to humans, but can be deadly for bacteria.
Phages work by penetrating the bacterial membrane and replicating inside the cell until it bursts open, killing the bacterium and releasing more phages. The key to harnessing them therapeutically is to find phages that are extremely efficient at killing the strains of bacteria causing particular infections.
In clinic, they can be inhaled through a nebuliser, sprayed on to the skin or taken orally, depending on the type of infection. To date, patients have typically been given bespoke therapies, but in future it is hoped that off-the-shelf cocktails of phages could be used to treat common infections, such as E coli and C difficile.
“I get fairly regular emails from doctors and patients wanting phages,” Clokie said. “Doctors have gone from being completely disinterested to ‘give me the phages now’ … There are people who need phages now because they’re dying.”
Clokie’s lab is preparing a phage cocktail for the doctor of a London-based patient with a chronic UTI, who is allergic to antibiotics and so does not have other treatment options. However, these one-off cases typically involve scientists spending months in the lab designing expensive, bespoke treatments.
“There’s always several months scrambling around trying to find the right phages,” she said. “The idea of having this systematic, well-curated collection is that … doctors will be able to access the right phages straight away.”
Students working in the lab at the University of Leicester. Photograph: Christopher Thomond/The Guardian
The lab already has a collection of about 2,000 phages stored in a freezer at -80C, and it hopes to increase this by about 1,000 samples each year. Phages occur ubiquitously in nature, but phage-hunting involves tracking down the ones that efficiently kill infection-causing strains.
“Wherever you have high numbers of bacteria, by definition you’ll have high numbers of phages,” Clokie said. “The most common place people look is human sewage.”
Clokie’s students have been sent out to dredge muddy estuaries and piles of horse muck in the quest for new species. A set of phages extracted from slime in a stream in Bradgate Park, Leicester, were found to be particularly good at targeting biofilms, which are often seen in chronic bladder infections and are among those under consideration for treating the London-based patient.
“It starts off incredibly low-tech,” Clokie said. But the advent of AI-based approaches means scientists are increasingly aiming to predict phage characteristics based on genetic sequencing, and how multiple phages might interact.
Petri dishes in the lab. Photograph: Christopher Thomond/The Guardian
Clokie said that despite a growing awareness of the threat of antibiotic resistance over the past decade, the outlook had not improved and doctors were reporting an expanding list of infections showing multi-drug resistance, including E coli, pneumonia, gonorrhoea and the stomach bug shigella.
A critical problem, she said, was the weak economic incentives for pharmaceutical companies to develop new antibiotics, given the increasingly restricted use of the drugs. In recent years, several companies have redirected R&D efforts into more lucrative areas such as cancer drugs, despite the growing threat of resistance.
“People will be cured of cancer but die of sepsis,” Clokie said. “There’s a really interesting disconnect between how much people are prepared to pay for drugs for autoimmune diseases or cancer and what they’re prepared to pay for antibiotics.”
Clokie is among those calling for an update to regulations created with conventional drugs in mind, to make it easier to carry out trials that could pave the way for wider use of phages. “At the moment, you need a willing doctor who is prepared to put phages into a patient as an unlicensed medicine and if something goes wrong they’ll get their licence removed,” she said.
In future, cocktails could be designed to treat common infections rather than specific strains in individual patients. Clokie said the growing use of phages in agriculture – as an alternative to chlorine spray in potato production – shows that costs are not prohibitive.
“They’re not going to replace antibiotics but they can be used to protect and preserve our antibiotics,” she said. “We can use them in chronic settings and we can use them in combination with antibiotics. I see it being a really useful complementary treatment.”
A proposed measure in Switzerland would have made that country the first to ban medical and scientific experimentation on animals. It failed to pass in February 2022, with only 21{bf0515afdcaddba073662ceb89fbb62b6b1bf123143c0e06b788e1946e8c353f} of voters in favor. Yet globally, including in the United States, there is concern about whether animal research is ethical.
We both place high importance on ensuring that animal research is conducted ethically and humanely. But what counts as “ethical” animal research in the first place?
The 4 R’s of animal research
There is no single standard definition of ethical animal research. However, it broadly means the humane care of research animals – from their acquisition and housing to the study experience itself.
Federal research agencies follow guiding principles in evaluating the use and care of animals in research. One is that the research must increase knowledge and, either directly or indirectly, have the potential to benefit the health and welfare of humans and other animals. Another is that only the minimum number of animals required to obtain valid results should be included. Researchers must use procedures that minimize pain and distress and maximize the animals’ welfare. They are also asked to consider whether they could use nonanimal alternatives instead, such as mathematical models or computer simulations.
These principles are summarized by the “3 R’s” of animal research: reduction, refinement and replacement. The 3 R’s encourage scientists to develop new techniques that allow them to replace animals with appropriate alternatives.
L’Oreal Brazil CEO Marcelo Zimet looks at microscope samples at the Episkin laboratory, which has developed alternative methods to animal testing. Mauro Pimentel/AFP via Getty Images
Since these guidelines were first disseminated in the early 1960s, new tools have helped to significantly decrease animal research. In fact, since 1985, the number of animals in research has been reduced by half.
A fourth “R” was formalized in the late 1990s: rehabilitation, referring to care for animals after their role in research is complete.
These guidelines are designed to ensure that researchers and regulators consider the costs and benefits of using animals in research, focused on the good it could provide for many more animals and humans. These guidelines also ensure protection of a group – animals – that cannot consent to its own participation in research. There are a number of human groups that cannot consent to research, either, such as infants and young children, but for whom regulated research is still permitted, so that they can gain the potential benefits from discoveries.
In the U.S., the Animal Welfare Act protects all warmblooded animals except rats, mice and birds bred for research. Rats, mice and birds are protected – along with fish, reptiles and all other vertebrates – by the Public Health Service Policy.
Each institution that conducts animal research has an entity called the Institutional Animal Care and Use Committee, or IACUC. The IACUC is composed of veterinarians, scientists, nonscientists and members of the public. Before researchers are allowed to start their studies, the IACUC reviews their research protocols to ensure they follow national standards. The IACUC also oversees studies after approval to continually enforce ethical research practices and animal care. It, along with the U.S. Department of Agriculture, accreditation agencies and funding entities, may conduct unannounced inspections.
Laboratories that violate standards may be fined, forced to stop their studies, excluded from research funding, ordered to cease and desist, and have their licenses suspended or revoked. Allegations of misconduct are also investigated by the National Institutes of Health’s Office of Laboratory Animal Welfare.
Above and beyond the basic national standards for humane treatment, research institutions across 47 countries, including the U.S., may seek voluntary accreditation by a nonprofit called the Association for Assessment and Accreditation of Laboratory Animal Care, or AAALAC International. AAALAC accreditation recognizes the maintenance of high standards of animal care and use. It can also help recruit scientists to accredited institutes, promote scientific validity and demonstrate accountability.
Principles in practice
So what impact do these guidelines actually have on research and animals?
First, they have made sure that scientists create protocols that describe the purpose of their research and why animals are necessary to answer a meaningful question that could benefit health or medical care. While computer models and cell cultures can play an important role in some research, others studies, like those on Alzheimer’s disease, need animal models to better capture the complexities of living organisms. The protocol must outline how animals will be housed and cared for, and who will care for and work with the animals, to ensure that they are trained to treat animals humanely.
During continual study oversight, inspectors look for whether animals are provided with housing specifically designed for their species’ behavioral and social needs. For example, mice are given nesting materials to create a comfortable environment for living and raising pups. When animals don’t have environmental stimulation, it can alter their brain function – harming not only the animal, but also the science.
Monitoring agencies also consider animals’ distress. If something is known to be painful in humans, it is assumed to be painful in animals as well. Sedation, painkillers or anesthesia must be provided when animals experience more than momentary or slight pain.
For some research that requires assessing organs and tissues, such as the study of heart disease, animals must be euthanized. Veterinary professionals perform or oversee the euthanasia process. Methods must be in compliance with guidelines from the American Veterinary Medical Association, which requires rapid and painless techniques in distress-free conditions.
Fortunately, following their time in research, some animals can be adopted into loving homes, and others may be retired to havens and sanctuaries equipped with veterinary care, nutrition and enrichment.
These advances also benefit zoo animals, wildlife and endangered species. Animal research has allowed for the eradication of certain diseases in cattle, for example, leading not only to reduced farm cattle deaths and human famine, but also to improved health for wild cattle. Health care advances for pets – including cancer treatments, effective vaccines, nutritional prescription diets and flea and tick treatments – are also available thanks to animal research.
Those who work in animal research share a deep appreciation for the creatures who make this work possible. For future strides in biomedical care to be possible, we believe that research using animals must be protected, and that animal health and safety must always remain the top priority.
Editor’s note: One photo depicting a species that is highly restricted for use in biomedical research has been removed from the article.
