- NON ANIMAL TECHNOLOGY - the future is amazing, and animal-free.
Technology is more valuable than animal tests
If we didn’t have animal testing, medical progress would stop. We would have no idea which medications were effective and which were dangerous until humans took them.
This is claimed by people who don’t understand animal experiments, and people who support them for financial reasons. The reality is that the technology available is incredible and enables achievements that few would have believed possible.
An excellent film on non-animal technology was made by doctors' group Safer Medicines. This is available to view online and comes very highly recommended.
You may also like to see our news page on medical progress.
Frustration at the slow pace at which technology is adopted has been voiced by medical professionals.
The concept that animal testing is neccesary is gaining more challenges in the media, such as here. Another article explains the neccesity of developing and using human-centred technology, as the animal methods are not predictive.
* Computer modelling
* Cell culture
* Brain research
Imagine that you try a drug on a mouse and it dies of a heart attack. You then have to ask:
* Did the drug actually cause the heart attack?
* What actually happened?
* Would it be the same in humans?
Computer models of the human heart are now in use. They enable us to watch the heart beat in 3D from all angles, and show reaction to a drug being used. You can then replay in slow motion what may happen and see what happened and why. The heart can develop illnesses and react to drugs, and since 2001 it has been used to identify dangerous drugs. (NewScientistTech. 2551 13 May 2006)
Other organs have been modelled too, and now there are even entire virtual humans. Yorkshire-based company Simcyp is producing software which predicts the effect of drugs, and accounts for the patients’ age, sex and height. A speciality is enabling predictions of drug effects in babies and children, a problematic area. (New Technology Detects Risks Of Drugs To Heart Sooner. Yorkshire Today, 2006)
Another key player is Physiomics, who claim they can help identify optimum dose levels, particularly for cancer drugs, accurately. The computer simulation it owns, SystemCell, uses biology and scientific data to simulate the way drugs will work in the body. (The Daily Telegraph. 19 August 2004)
The virtual heart has to be seen to be believed. An online video is available here.
The concept behind cell culture is simple, but the degree to which it has evolved is incredible. In 1996 the techniques available then were evaluated alongside animal tests, and the cell culture ones were found to be more accurate. (Clemedson C, McFarlane-Abdulla E, Andersson M, et al. MEIC Evaluation of Acute Systemic Toxicity. ATLA 1996;24:273-311)
Since then, cell culture use has expanded. The American National Cancer Institute (NCI) has developed a screening project to identify cancer drugs using only cell culture methods. NCI explains that “This project is designed to screen up to 20,000 compounds per year for potential anticancer activity. The operation of this screen utlilizes 60 different human tumor cell lines, representing leukaemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate and kidney.” (http://dtp.nco.nih.gov/branches/btb/ivclsp.html)
Previously, drug screening has been in animals. A textbook concludes that: "despite 25 years of intensive research and positive results in animal models, not a single anti-tumour drug emerged from this work." (JCW Salen, Animal Models-Principles and Problems in Handbook of Laboratory Animal Science 1994)
June 2010 - news item on cell culture - click here.
Dec 2010 - cell culture dug trials of cancer drugs are quicker and more effective than animal tests - read more here.
March 2011 - The damage of Parkinson's Disease can now be observed in a cell culture - read more here.
June 2011 - As a doctor explains, animal tests are inferior than any of the technological technology tests. click here.
June 2011 - Experts are building a computer-based genetic model in which colon cancer treatment will be tsted on a personal level. Click here.
November 2011 - 'Micro lungs' built from lung and liver cells will enable more accurate testing. Read more here.
February 2012 - Nanosensers enable testing of chemicals. Read more here.
February 2012 - Swansea University search for better methods. Read more here.
May 2012 - Analytical chemistry replaces mice in Food Standards test. Read more here.
June 2012 - China approves a non animal technique for cosmetics ingredients. Read more here.
July 2012 - $70 million project to develop 'organ on a chip' technology. Read more here.
Skin and eye safety
Skin testing has long been a common use for animals, although various cell culture tests exist. EpiDerm uses human skin cells and is accepted as accurate, while Epipack uses sheets of cloned human skin cells. The Human Keratinocyte Bioassay enables a computer to measure damage to the epithelial cells, which cover the skin and eyes. Corrositex detects skin damage using a membrane and a chemical detection fluid, and gives results in 4 hours – compared with 4 weeks for animal tests. (www.mbresearch.com)
Eye damage can be assessed using MatTek EpiOcular (see the diagram below). Since 1985 this model has been using human cells to evaluate eye irritancy. Valuable as this is, the test is not isolated and other models are being developed. (www.mbresearch.com 31/12/2006)
Interestingly, the SkinEthic and MakTek cellmodels were approved by European regulators which means the much discredited Draize rabbit test is officially obsolete.
New applications are always emerging - such as Toxcast
Another is InLiveTox, an artificial liver and gut.
Tox21 was discussed in August 2010 as a much more reliable and fantastically more speedy method than animal testing to reveal drug safety and efficiency.
Another area is biochips. An 'Artery-on-a-chip' has been developed, which is a microfluidic platform on which fragile blood vessels can be fixed, allowing the factors that promote and sustain cardiovascular diseases to be studied.
Teratology – or the study of the cause of birth defects is an area where animal tests are clearly inferior to other available methods (Biogenic Amines Vol. 19, No. 2, pp. 97–145 (2005)) (see our page on this - LINK). The Embryonic Cell Test (EST) is a highly accurate test, and the Micromass (MM) test is proven particularly effective for chemicals causing specific forms of damage to the growing embryo, emphasizing the value of cell culture tests in this area too. (Biogenic Amines Vol. 19, No. 2, pp. 97–145 (2005))
Their conclusions show that the dilemma is not between animal tests and cell culture, but a decision between cell culture and human experience: “virtually every substance or dietary deficiency currently recognized as being teratogenic in humans was initially identified as a result of case reports and clinical series”. (Polifka, J. E. and Friedman, J. M. (1999). Clinical teratology: identifying teratogenic risks in humans).
Microdosing is so incredible it sounds like science fiction. In reality it is the incisive use of technology to safely study medications in the ideal model – a human patient.
It involves tiny doses of a test medication being given to a patient, who is then scanned in detail using sensitive imaging equipment. This helps to accurately identify the route of the drug, and the organs or other tissues that it affects. The appeal of the technique is safe because the doses involved are so tiny (typically about 1% of clinical levels) that damage will not be caused. The technique enables the drug to be tested in an intact living system without resorting to use of a different species.
The method works by ‘labelling’ the drug using a carbon isotype, which enables it to be traced. The conversion of the drug into other molecules can then be measured, and the length of time they stay in the system can be assessed.
Does it work?
Concerns were made that low dose drugs would behave different from the full dose. To counter, an independent test was invited by Xceleron, a pioneer of the technique formed from York University. Drugs known to have unusual characteristics that animal testing failed to detect were examined using microdosing. An accuracy rate of 70% was achieved when results were compared with full-dose studies.
Considering that animal studies typically achieve lower accuracy rates, and that this test was for drugs known to harbour idiosyncrasies, the success is remarkable. The American drug regulator FDA has now said it will accept microdose data.
Evidence that the technique can work at doses even lower than 1% was revealed by American group Radiant Research, who re-evaluated HIV drug AZT at one millionth (0.0001%) of its usual dose. More than 72 hours after administering the drug they were able to evaluate concentrations in blood, saliva, urine, DNA and white blood cells. The accuracy is stunning: an expert explained "we can say with confidence that between 30 min and 45 minutes after dosing, 0.09% of the oral dose resided within the white blood cells in the blood. We were also able to show uptake of AZT into the genetic material of these cells, which is ultimately how antivirals like AZT inhibit viral replication. Such data could not have been obtained by any other method".
The technique is possible thanks to Accelerator Mass Spectrometry technology, coupled with PET scans to see where the drug travels in the body. AMS is so incredibly sensitive that it enables analysis at levels previously impossible. Thanks to microdose technology, drug research will never be the same.
European regulators have concluded that the technique will “make human clinical studies safer”; until now they have relied largely on animal studies. They could also save money. An industry publication stated that it “…should allow better choices to be made in drug development, focusing resources on drug candidates that are more likely to succeed and killing early those compounds that will sap resources and waste time.”
Microdosing could also develop the area of personalised medicine. Some drugs may be safe or effective in many patients, but useless or damaging in others. People have died due to unexpected reaction caused by otherwise safe medical drugs.
"The individual response to drugs can vary tremendously", says an expert. "Some of this behaviour can be explained through metabolic signatures in the individual. Accelerator Technology enables such profiling."
Microdosing promises not only to make existing processes safer and more accurate, but also to unlock areas of medicine we only dreamed of in the recent past.
June 2011 - This article in a leading medical journal details the calls for routine personalised medicine.
December 2011 - This article explains how personalised medicine can revolutionise cancer treatment.
December 2011 - The Mayo Clinic (USA) is developing a landmark project to advance this form of study.
The cells of life
Test on an animal and immediately you’re faced with the complexities of an intricate living system, and identifying the effect on different organs is unfeasible. It is now more obvious that disease works on at the level of individual cells, so understanding the different cell types is essential.
This is leading to the rise of proteomics. This exciting area of science studies the activity of proteins in the cells: how, in the normal cell function, proteins function and are regulated - and what happens to cause illness. The proteome is defined as the constellation of the proteins in a cell. The arrangement of them and which ones are present is a matter which has massive consequences for health. This is because proteins build most cell structures and perform most of the functions which are needed for life to function healthily. “Proteins are central to our understanding of cellular function and disease processes and without a concerted effort in proteomics the fruits of genomics will go unrealised. The necessity of proteomics cannot be avoided” - says an expert in the field. (www.xensei.com/users/chi/2001/hpr/hpr_pressrelease.htm)
Catalogue the proteome
Plans to catalogue proteins have started in a similar way to the human genome project. Just as genes and their roles are understood far better thanks to study of the human genome, plans to investigate the human body’s proteins are underway. The benefits of proteomics are likely to be in complex diseases like cancer, and those of the cardiovascular system. Already advances have been made; a protein called HER3 has been studied and the three-dimensional structure in now known. Before this, it was almost impossible to predict how drugs will bind to the protein, but experts now predict they will be able to prevent or treat specific cancer types by targeting HER3. (John Hopkins Medical institutions Press Release Aug 6th 2002 “Structure of key receptor unlocked; Related proteins will fall like dominoes”)
Hopes were raised in the area of HIV treatment when it was discovered that a gene prevents HIV from reproducing, but is blocked by a single protein. This could lead to a whole new type of HIV treatments. (Thomas Jefferson University Information Release 8th July 2002 “Discovery may lead to new HIV drugs, says Jefferson virologist”)
There are big plans for proteomics - read more here.
“With so many pre-clinical systems that are much more reliable than animal research now available, the only reason I can see to use animal experiments is this: there is need to think when doing such experiments. Killing animals is so much more congenial than thinking for some ‘scientists’ that animal research remains popular.” (Irwin D Bross, PhD, former Director of Biostatics at the Roswell Park Memorial Institute for Cancer Research)
Technology in the modern laboratory
fMRI (functional Magnetic Resonance Imaging) This technique identifies the role of different areas of the brain. It does this by detecting higher and lower magnetic susceptibilities in the blood, which indicate whether the blood is newly oxygenated or not. Real time scans are possible which aid treatments such as surgery and are of great value as a diagnostic tool.
MagnetoEncephaloGraphy (or MEG) detects the magnetic fields associated with brain activity without using X-rays. It sends no signals into the brain so is entirely safe. It enables a functional image of the brain to be shown. This helps show what activity the brain is undertaking, and where in the brain this comes from. It helps show where problems (eg epilepsy or migraine) is coming from.
See this link for a UK university working at the forefront of this technology. Or see this work at Aston University and these projects there for some of the valuable work now being conducted in humans.
EIT (Electrical Impedance Tomography), is mobile and cheap. It registers electrical resistance in disease-affected areas. The main benefit is therefore to trace the movement of blood and other fluids. Developments will hopefully lead to this being a cheap, portable method of imaging the brain in full 3-D detail.
See this link for the detailed interpretation of info from EIT, and this for more applications.
SPECT (Single Photon-Emission Computed Tomography) enables doctors to build 3D images of the brain by detecting details about the flow of blood. This shows brain function and is vital for detection of illnesses. This is done by radioactive labelling blood.
Powerful new microscopes and other technologies make studies of actual human tissue very valuable to serious researchers, while making animal research obsolete.
SPECT scan showing details of a patient's stroke.
PET (Positron emission tomography) scans detect radiation from positrons, and enable a detailed picture of the illness to be constructed. This is vital for patients with brain dysfunction for which the cause has not been determined.
MRS (Magnetic Resonance Spectroscopy) Enables chemical analysis of the brain without surgery, by distinguishing the chemical nature of the part of the brain being scanned. This is done by detecting the magnetic resonance in that part of the brain and analysing the data this shows.
EROS Uses lasers which can pass through the skull, to image the brain. They are fired from dozens of different directions at once, and the technique measures differences in the way they reflect. The differences are caused by the fluid in the brain cells, and reveal vital information about the condition of the different parts of the brain.
TMS (Transcranial magnetic stimulation) stimulates or calms parts of the brain using magnetic impulses. Higher frequencies stimulate, lower ones calm. This enables doctors to calm brain areas and assess the affect on symptoms, therefore identifying brain areas linked with specific illnesses. Long-term imbalances in the brain can be identified.
See more here, here or here.
Without autopsies, the progress in neurology would be almost non existent. This method has focused on real patients and the real nature of their brains, and full records of their condition have been compared with the findings. As microscopes become more powerful, the method becomes more effective.
Studies have shown that the same areas in different animal and human brains play different roles as well: damage to the corresponding parts of monkey and human brains has been shown do cause different symptoms. (Reymond in Comparative Primate Biology (vol 4): Neurosciences, by H. S Steklis and J. Erwin, 1988, p605. Dr Hepp-Reymond in Comparative Primate Biology (vol 4): Neurosciences, ed by H. S. Steklis and J. Erwin, 1988 p605)
In the early 1800s the speech centres of the brain were located through autopsies and observing patients – work which would have been impossible through vivisection as animals lack the same speech process more obviously than they lack other processes.(Neurology 1981;31:600-02)
Research into human brain function is only really possible through studying humans – either in life or at post mortem. As a recognised neurologist explains:
“The study of the brain, if it is to bear fruit, must be made on man, i.e. at the bedside and in the post-mortem theatre; …The utmost that can be learned from experiments on the brains of animals is the topography of the animal’s brain, and it must still remain for the science of human anatomy and clinical investigation to enlighten us in regard…of our own species; and in fact, it is from the department of clinical investigation and post-mortem study that so far all of our best brain localizations have been secured.” (Jean Martin Charcot, Quoted in ‘Clinical Medical Discoveries’, Bayly, B, NAVS London, 1961, p27)