Stand Up for Science

Exciting “new” breast-cancer drug progresses to human trials

Author: Dr Imre Hunyor, guest writer on standupforscience

One purpose of this blog is to highlight the ever-increasing number of scientific findings that illustrate the benefits of animal testing for human health. Not all of us have time to digest the intricacies of peer-reviewed scientific journals and are forced to rely on the popular press to tell us about the latest medical research. Often, the reliance on animal testing is assumed and not reported.

This week, human trials have begun using a previously known anticancer drug, carboplatin, which could transform anticancer treatment for women who develop breast cancer as a result of a common genetic mutation (Reference 1 & 2). Carboplatin has been around for a long time and is often used in the treatment of lung and ovarian cancers, but has not been tested in the subset of breast cancer caused by mutations in the genes BRCA1 and 2 (present in about 5% of breast cancer patients). Carriers of a mutation in BRCA1 are thought to have a 50 to 85 percent lifetime risk of breast cancer and a 20 to 40 percent lifetime risk of ovarian cancer. Women with a mutation in BRCA2 appear to have a similar risk of breast cancer and a 10 to 20 percent risk of ovarian cancer (3).

Cancers are well known to arise from DNA mutations, so mimicking this in animals makes for a viable and accurate model. The key issue I would like to highlight here is that researchers had been able to create the genetic mutation in a breed of mice (4), and thus test carboplatin in this animal model of human disease. The rodent model demonstrated that cells with a mutation in the BRCA gene are more sensitive to carboplatin compared with normal cells.

Following confirmation in other laboratory experiments and pre-clinical trials, human clinical trials of carboplatin in patients with breast cancer and the BRCA1/2 mutation are now underway. Previous animal studies and years of use for the treatment of other cancers in humans have the allowed rapid progression to human clinical trials.

Animal testing is not a guarantee of a successful outcome in humans – but our understanding of breast cancer and the discovery that carboplatin could be effective for a subgroup of patients with the disease was possible through investigations involving animals.

(1) An excellent website describing the current trial and its scientific rationale (far more detailed than in this blog) can be found at http://www.geneticbreastcancertrial.usilu.net/Home.html
(2) Lung cancer drug may fight breast tumour in women, The Times, May 1, 2006. http://www.timesonline.co.uk/article/0,,2-2159380.html
(3) Haber, D. Prophylactic oophorectomy to reduce the risk of ovarian and breast cancer in carriers of BRCA mutations. N Engl J Med May 23; 346 (21) 1660-2 (2002)
(4) Fedier, A., et al. The effect of loss of brca1 on the sensitivity to anticancer agents in p53-deficient cells. Int J Oncol 22, 1169-73 (2003).

Macaque Studies Find Potential AIDS Preventative Treatment

Recent studies in monkeys have found that a combination of two drugs already approved for use in humans and present in pharmacies everywhere, appear to help prevent HIV transmission.

The two drugs are known as tenofovir and emtricitabine, appear to prevent transmission if taken prior to exposure. The scientists still don’t know the time frame that the drugs may need to be taken prior to exposure, or if they could be taken after exposure, but the investigation is still in early stages.

The drugs could be given to people at high risk for infection, including women in Africa, at risk of being infected by their HIV positive partners.

Six macaques were treated with the drug combination and exposed for 14 weeks to a combination of the human and monkey AIDS viruses. Not a single one contracted disease. On the other hand, all but one of the monkeys not treated, contracted AIDS.

Even after the drugs were stopped, (as well as the AIDS exposure), the monkeys have remained healthy and tested negative for AIDS. It looks like macaques may be helping scientists to find effective, preventative measures against HIV and AIDS!

Recent Breakthrough in Medicine Thanks to Animal Research!

Potential Future Treatments for Spinal Cord Injuries

When spinal cord injuries occur, the nerves that are injured can cause further damage to healthy neurons due to a process called demyelination. But studies conducted by scientists on 97 rats found that transplantation of specific cells of the rats own brain soon after the injury (two weeks), led to a gain in coordination and the ability to bear weight on their hind limbs. While previous studies have shown similar results, the difference is that embryonic cells weren’t used but the animals own neural precursor cells.

The animals didn’t recover the ability to walk completely normal, but the results were very promising. They hope that this could also be done in humans one day. One current obstacle for these scientists though, is finding a way to treat those who have been paralyzed for much longer than 2 weeks. When the researchers transplanted the cells in mice with 8 week old injuries, they didn’t see the marked improvement in the mice they had seen with the transplants at 2 weeks. Looks like the researchers will have their work cut out for them, but thanks to their hard work and dedication, maybe it will lead to a treatment for paralysis one day!

The original journal article is:
J Neurosci. (March 29 2006) 26(13):3377-89 Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG.

Why Animal Research is Important AND Needed: A Copy of the Speech I Gave on the February 25th Demonstration

I’m here today to represent students and stand up for what I believe in. We are here to celebrate progress, the pursuit of knowledge and the achievements of medical research that requires animal testing. We are here to support scientists and doctors who are working to save each and every one of us from disease and suffering. We seek to inform the public and are here to encourage rational, open and peaceful debate.

Without research involving animal testing we wouldn’t have insulin to treat diabetes. We wouldn’t have antibiotics for infections, vaccines to prevent disease and surgeries to treat the injured. If this fundamental research is stopped, we won’t find a cure for cancer, a treatment for Parkinson’s disease, a vaccine for AIDS, a therapy for Alzheimer’s and a cure for paralysis. ANY further advances in medicine and human health are absolutely dependent on animal research.

Right here in Oxford, countless medical advances have been made – most have required some level of animal testing. These include the discovery of penicillin, treatments for hemophilia and childhood leukemia, and the development and trials of vaccines for meningitis in children. Oxford has helped contribute to our understanding of heart disease, cancer, bird flu, infectious diseases and numerous other illnesses. And if we are able to continue our research with animals, we can help find cures for these illnesses.

Whether these diseases affect us directly or someone we love, we want to know that researchers across the world are working towards a cure. Unfortunately, there are people who want to stop medical progress and are using a variety of tactics to publicize their message from mild to extreme and life threatening. But I’m here today to show that research will not be STOPPED and that humanity will continue to look for ways to improve the quality of our lives. I, like every reasonable person, am all for the ethical treatment of animals – However I also recognize that in order to treat human suffering and advance medical science, animal testing is a necessity.

We all need to be worried for our future if we don’t stand up and support the people saving lives with their research in animals. We cannot let the advancement of knowledge be halted as it was in Cambridge. Progress and the pursuit of knowledge CANNOT be stopped and WILL NOT be stopped, and the proof of it lies in front of me. Let’s stand up for reason, let’s stand up for our rights, and let’s DEMAND that the Oxford lab be constructed without interference and intimidation.

Facts about Animal Research

Here are some of the facts I researched about animal research. (They are also posted up on the PRO-Test website.)

Benefits

Without animal research, medicine as we know it today wouldn’t exist. Animal research has enabled us to find treatments for cancer, antibiotics for infections, vaccines to prevent some of the most deadly and debilitating viruses and surgery for injuries, illnesses and deformities.

According to the US based, Foundation for Biomedical Research: “Animal research has played a vital role in virtually every major medical advance of the last century - for both human and veterinary health. From antibiotics to blood transfusions, from dialysis to organ transplantation, from vaccinations to chemotherapy, bypass surgery and joint replacement, practically every present-day protocol for the prevention, treatment, cure and control of disease, pain and suffering is based on knowledge attained through research with lab animals.”[1]

But animal research hasn’t benefited humans alone. Animals also have improved healthcare and a longer lifespan. Farm animals, household pets, wild species and endangered species are all benefiting from the research conducted through animals. There are vaccines for rabies, distemper, tetanus, parvo virus and numerous other illnesses in cats, dogs and countless other domesticated animals. Cats now have a treatment for Feline Leukemia. It’s obvious that animal research benefits all living species and that we are all able to live longer, healthier, happier lives because of it.

In fact, seven out of the ten most recent Nobel Prizes in medicine, were based on animal research. Here’s a link citing a list of 71 of the Nobel Prizes won in the last 103 years using animal models, including what animal they used.

Examples of the Benefits from Animal Research and the Animals Involved:

Smallpox (cow) has now been eradicated from earth, Polio has been eradicated from North America and people in countries all over the world are being successfully treated (mouse and monkey). Insulin is now able to help control diabetes (dog, fish). There are vaccines for tetanus (horse), rubella (monkey), anthrax (sheep), and rabies (dog, rabbit). A short list, far from comprehensive, of some of the achievements made possible by medical research and the animal used to develop it[2]:

An understanding of the Malaria lifecycle (pigeon), tuberculosis (cow, sheep), Typhus (guinea pig, rat, mouse), and the function of neurons (cat, dog).
The discovery of anticoagulants (cat), penicillin (mouse), open heart surgery and cardiac pacemakers (dog), lithium (rat, guinea pig), treatment for leprosy (armadillo), organ transplantations (dog, sheep, cow, pig), laproscopic surgical techniques (pig), and a drug for AIDS treatment (monkey)

Number of Animals Used
The number of procedures and experiments involving animals in 2004 for the United Kingdom was exactly 2,854,944. The number of animals used is slightly less than this because some experiments used a particular animal more than once.[3]

In the UK in 2004, the a wide variety of institutions used animal research. The percentages of each are as follows: universities (42.1 %); commercial organizations (33.3 %); non-profit organizations (4.9 %); government departments (2.4 %); National Health Service hospitals (0.9 %); public health laboratories (0.6 %); other public bodies (15.8 %).[4]

The Types of Animals Used
The animals used for research in the United Kingdom must be specially bred by registered license holders. Research is not performed on stray animals or unwanted pets. This is strictly illegal. The use of chimpanzees, orangutans, and gorillas is also banned. The majority of research is conducted on rodents, with a smaller percentage using fish, reptiles, and birds. A very small percentage is conducted in larger mammals. The exact percentages for animals used in the UK in 2004 were[5]:

84% Rats, mice and other rodents. All specially bred laboratory species
12% Fish, amphibians, reptiles and birds (including many fertilised hen's eggs)
1% Small mammals other than rodents, mostly rabbits and ferrets
2.6% Sheep, cows, pigs and other large mammals
0.3% Dogs and cats. Specially bred for research. No strays or unwanted pets can be used
0.15% Monkeys, such as marmosets and macaques. Chimpanzees, orang-utans and gorillas have not been used in this country for over 20 years and their use is now banned.

Alternatives

One of the most common questions asked is why scientists don’t use alternatives to animals.

Living organisms are incredibly complex and scientists still only understand a very small fraction of the structures, chemicals, interactions and metabolic pathways in humans and animals. The only way for scientists to learn more about them is through organisms that possess these traits. That’s why animal research is so important for the future of medicine and the ability to treat and cure diseases.

What few people realize is that multiple tests involving cells, DNA, proteins, and in-vitro techniques are used in the initial stages of biomedical research. It’s only when a point is reached where no experimental model can be substituted for a living organism.

When working to learn new information in science, the process starts at the smallest level possible. This is often work done with DNA from cell lines or the proteins that cause disease. As scientists and researchers learn more about their topic, the level of complexity increases in the models they study. They may move on to bacterial cells, then mammalian (animal and human) cells, then into entire organs and eventually into animals. We don’t currently have the technology to make computer programs or other methods of replicating the intricate and highly sensitive models that an entire living animal provides us with.

So asking why alternatives aren’t used is a misleading question. The experiments used that aren’t performed in animals are complementary to the experiments performed in animals and help researchers understand the big picture of a disease or system.

If there are any methods that can be used before an animal to learn new information, British law dictates they must be used.

Types of Animal Research

Animal research falls under three broad categories[6]:
1. Pure research
2. Applied research
3. Toxicology research

Medical Research Council

The Medical Research Council was established in 1913 in order to study diseases and illnesses and look for ways of treating or curing them.

As they explain in their informational booklet, they study diseases through multiple models to best understand the mechanisms involved in the health aspects they research, using humans, cell cultures and animals.

Thanks to the recent genomic revolution, sequencing of the human genome and many animal genomes, they now have a much greater understanding of which particular species share similar or different aspects of the human body, allowing animal research to become much more specific and targeted. It has enabled scientists to make educated decisions on which animals will serve as excellent models of varying diseases.

The MRC states that approximately 30% of their research uses animals and the remainder of studies conducted are in other models, like those listed above.[7]

Frequently Asked Questions (FAQ)

If animal research prevents toxicity effects in humans from new drugs, what happened with thalidomide?

One of the major arguments against testing drugs on animals is the example of the drug thalidomide, known to chemists as (±)-N-(2,6-Dioxo-3-piperidyl)phthalimide, that caused birth defects. Thalidomide was introduced in 1956 and marketed as a sedative. Within several years, its use had spread around the world and women began taking it to help combat the nausea associated with pregnancy. In 1961, several physicians linked thalidomide with birth defects observed in their patients currently taking it. Almost immediately after, physicians worldwide began confirming these results. Soon after the discovery of the teratogenic effects became known, it was taken off the market.

Thalidomide did initially pass safety tests in animals because the proper tests were not performed, namely testing thalidomide in pregnant animals. If a through battery of tests had been performed in animals, the teratogenic effects would have been caught. Those opposing animal research though, cite Thalidomide as the perfect example to show why animals cannot be used to replace humans. They claim that Thalidomide did not cause birth defects in animals, only humans, which is completely inaccurate. Once the drug was pulled off the market, additional tests in animals were done, and it was found that mice, rats, hamsters, marmosets and baboons all suffered similar effects as observed in humans. (See original literature below)

Another note is that thalidomide was never approved in the USA because the Federal Drug Administration (FDA), felt there was too little data to prove its safety, and wanted additional tests.

Part of the reason less animal tests were performed is because of lax regulations and a more limited knowledge of medical science. What wasn’t realized at the time, was that if a pregnant women suffered no side effects, neither would the fetus. This was also believed to be the same with animals. Medical research has now shown this to be false, as most medications of any kind need to be avoided during pregnancy unless absolutely necessary.

Ultimately, the sales of thalidomide with insufficient pharmacokinetic data lead to the tragedy of an estimated 15,000 fetuses suffering birth defects. The ones who suffered from this situation were not the animals, but thousands of women who lost unborn children. Those children who did survive suffered from massive disfiguring deformities.

Thalidomide only serves to highlight the inadequacy of the testing process at the time, not the inadequacies of animal testing. This misfortune could have been prevented had we conducted through animal tests, including pregnancy studies. A few more animals and countless human lives would have been saved.

Fortunately, scientists and the medical community have learned from past mistakes. Laws and regulations have been revised and made much stricter. The tests conducted today before a drug is made available to the public finds teratogenic effects as well as numerous others. Time and time again, animal testing has proven its record as serving as an excellent indicator for how a drug will react in the human body.

Some of the original journal articleson the research of Thalidomide:

1.Blake DA, Gordon GB, Spielberg SP. The role of metabolic activation in thalidomide teratogenesis. Teratology 1982;25(2):28A-29A.).
2.DiPaolo JA (1963). Congenital malformation in strain A mice: its experimental production by thalidomide. JAMA vol.183: 139-141
3.Homburger F, Chaube S, Eppenberger M, Bogdonoff PD and Nixon CW (1965). Susceptibility of certain inbred strains of hamsters to teratogenic effects of thalidomide. Toxicol Appl Pharmaco vol.: 686-69
4.Hamilton WJ & Poswillo DE (1972). Limb reduction anomalies induced in the marmoset by thalidomide. J Anat vol.11:505-50
5.Hendrick AG, Axelrod LR & Clayborn LD (1966). Thalidomide syndrome in baboons Natur vol. 210: 958-95
6.King CTG &; Kendrick FJ (1962). Teratogenic effects of thalidomide in the Sprague Dawley rat. The Lancet: ii: 1116
7.Rajkumar, SV (2004). Thalidomide: Tragic Past and Promising Future Mayo Clin Proc. 79(7).

Animals are different from humans, so how can they accurately represent humans?

Animal models are not perfect representations of humans and scientists are well aware of this. BUT, they do serve as excellent substitutes (mostly using mice, rats and other small rodents) for humans.

As the genomic revolution has come around and the genomes of both humans and animals have been sequenced, we have realized that there are much more similarities between humans and animals than there are differences. It has also enabled us to identify where humans and particular animals are identical, as some animals serve as accurate representatives of a human’s anatomy, while others may share identical biochemical pathways. Genomic knowledge has made it so that animal research can be much more specifically targeted and accurate when representing a human, thus correctly predicting a how a human will react.

For example, mice are one of the most commonly used vertebrate species in animal research. This is because they small, easy to care for and for animal researchers to handle and work with and importantly, they reproduce much faster than many larger animals, as they can produce up to 100 babies in a year. This is an important trait when researchers are studying heritable diseases or compounds that could cause birth defects (see question number 1 on thalidomide). Mice are actually considered the best model of inherited human diseases. This is because they share 99% of all the genes with humans! Their genomes are also easy to manipulate to replicate the human form making them even more similar to humans[8].

What about cosmetic testing? Where does PRO-Test stand on cosmetic testing?

Cosmetic testing is banned in the United Kingdom. It is also banned in the Netherlands and Belgium, and the European Union has passed legislation that outlaws animal testing in the year 2009. By 2014, products still being tested on animals in other countries will also be banned in the EU[9].

Seeing as cosmetic testing is outlawed, PRO-Test does not need to take a stance on cosmetic testing. It is a non-issue. We also feel that it is currently irrelevant to our main goals as we are trying to promote research in animals to further medicine, health and science.