Think of a world where more new medicines are available more quickly, more safely and with few, if any, animals used in research. Think of a world where you know for sure that the drug you are prescribed is safe for you. This is what researchers at some of the world's leading universities are trying to bring about.
Academics from disciplines as far apart as computer science and biology are growing mini-human hearts in a lab or creating a model of the human biological system on a common computer chip. Their aim is to bring to an end to what has been called the "pharmaceutical ice age", an era of ever more research but fewer medicines reaching the shelves of Boots.
According to the
For some, the fault for this freeze is due to the pharmaceutical industry's obsession with mergers and acquisitions or a culture that inhibits innovation. For others, it is a sign that perhaps there just aren't many chemical compounds that can interact with the body and have a positive effect; or even that the tools scientists use during discovery and early-stage testing mean the wrong drugs go to human trials.
While animal testing is a regulatory requirement for any new drugs, it remains a fairly unpredictable guide to how a drug will react in humans. Testing drugs on cells in a petri dish allows much higher dosages than with an animal, but is an unreliable guide as to how they might interact with the human body. Virtual computer models of the likely impact of a drug have also, up to now, largely been based on the reactions of a single cell.
Now scientists are trying to use new technology to make drug testing faster, cheaper - and more accurate - by modelling more closely how a chemical interacts with the human body. They hope to do this to the point where a drug could be declared safe for a certain section of the population or even personally safe for you.
"Over the past 15-20 years, there has been a dramatic increase in results from biomedical research," says
"The problem has been that the discovery of new drugs hasn't been given as much like-by-like value by analysts as the development of drugs that can shift the share price," says Professor S John Lyon of
The tag line for the
The chips have fluid flowing through them, so you can connect them to each other, creating a "human on a chip" where lungs, livers, intestines, skin, kidneys and eyes can be integrated to simulate how a whole body would interact with a new drug.
"You could write a 2,000-word article just on this pharmaceutical ice age alone," laughs TED speaker Dr Geraldine A Hamilton who works with Ingber to develop the technology and commercialise it.
"The structures you find yourself working in can stifle innovation. Every time companies merge, productivity goes down. Then there has been a problem with the tools they use. Often, cells are put in a simple petri dish, but they live in a complex dynamic organic environment. Different animal species may give you different answers as to whether a drug is toxic for humans. Which one do you trust? Many good drugs are lost at that point.
"So we recreate the conditions the cells find themselves in by using micro-engineering to provide them with all the cellular integration, fluids and even mechanical forces that they are used to, such as breathing in and out. We can also connect them in our human bioemulation platform to model and better understand diseases, and to study how humans respond to drugs."
Until now, the complexity of chips meant they had to be made by hand, limiting their numbers. It also introduced variability, whereas they need to be reproducible and robust. So, in partnership with
Meanwhile, in the labs of
"Mini hearts are much better than using animals to test drugs - they are closer to the real thing and they should speed up the time it takes to move towards clinical trials," says Zhelev.
Far away from the petri dishes and lab coats, but just around the corner from
Rather than moving their research into the private sector, they have decided to stay within the university and will release their software free for academics in September and in due course it may be licensed as an app to the pharmaceutical industry.
"It is exciting to feel that you are exploring a genuine frontier," says PhD student
Virtual computer models comprise a large collection of equations that describe how components of a cell interact with one another and with physical quantities such as the voltage of the cell's membrane or concentrations of chemicals such as calcium and potassium.
"We solve these equations using computers and doing this allows us to simulate how a heart cell might behave in different conditions," says Britton.
"A lot of scepticism about the accuracy and usefulness of virtual models comes from a misunderstanding of how they should be used," says
"So we came up with this idea of using a population of varied models," says Britton. "This was the key step, as we can achieve more accurate results by first generating lots of different models of a human heart cell, then simulating how they would behave in control conditions and then discarding those that don't fit the range of experimental data we have available."
Seagrove warns that it is "a long way off" before any of these technologies are accepted instead of animals. The problem, he says, is that predictions about the impact of a new drug are built on existing evidence. "So you don't know what you don't know, and you don't know how a chemical will behave in a body until you do it."
"If you think about it, a pill is swallowed to get into the intestine, absorbed through the gut and then has to get to where the disease is, whether in the brain, eye or lungs. So during this process chemicals are exposed to proteins, enzymes and cells so it is hard for any technology to predict reliably how it will interact with human body."
He accepts these technologies mean we should get there quicker and so the more technology is available the quicker the process will be, and the easier it will be, to put your effort into promising candidates for new medicines. "If you are going to fail, fail early," he says.
The drive to melt the ice age has also encouraged the development of new approaches such as those that use DNA and human proteins. In June, the
Perhaps the ice age is ending.
Mice make up more than half of all vertebrates used in research within the EU. They are easy to breed and handle and share 95% of their genome with humans, including many genes responsible for diseases such as atherosclerosis and hypertension.
Comparable to humans in size and anatomy, pigs are often used for testing surgical procedures and implanted medical devices. They have similar hearts and skin to humans, making them suitable for dermatological studies and testing coronary stents.
These tiny tropical fish have a genome remarkably similar to humans. With fewer ethical and regulatory barriers in place, they have become popular with researchers investigating a range of conditions from Alzheimer's to leukaemia. Zebrafish are transparent, so it is often possible to observe directly biological processes as they occur.
Tighter regulation and more readily available alternatives have caused testing on primates to plummet in
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