Animal Testing

Animal testing (also known as vivisection) elicits strong opinions from both those for and those against the practice. Its role in developing HIV treatments and AIDS vaccines is no less controversial.

Developing therapeutic and diagnostic products for use in humans is a long and complex process. With HIV infection, the search for effective drugs and vaccines has proven particularly difficult, as HIV is exceptionally good at changing its structure and evading destruction. In an ideal world, scientists would be able to test thousands of different compounds on human participants to see if any cured, treated or vaccinated them against HIV. However, to do this would be both highly time consuming and dangerous, as most compounds would not be effective, and some might cause illness or even death.

Researchers therefore often use animals to help them test the efficacy of drugs and vaccines, and to make sure that these products are safe. There are of course many ethical implications to animal experimentation, and many people are strongly opposed to the use of animals in any sort of experiment or study that may cause them distress or harm. So is it really necessary to use animals in the production of HIV drugs and vaccines? And are there any alternatives to animal testing?
Why are tests performed on animals?

There are three reasons why animals may be used in scientific experimentation. The first is to ensure the safety of new drugs and other pharmaceutical products. The second is to see whether such products might be effective in humans. The third is for general research into the biology of an animal, or the function and action of certain diseases within its body.
Safety trials

In many countries it is a legal requirement that all drugs and vaccines (not just for HIV) are tested on animals to ensure safety. In the United Kingdom for example, the Medicines Act of 1968 1 states that all new pharmaceutical products must be tested on at least two different species of live mammal, one of which must be a large non-rodent. This legislation was introduced shortly after the discovery that the drug Thalidomide could cause serious physical deformities in babies born to mothers who had taken it during pregnancy. Thalidomide was not thoroughly tested on animals (particularly pregnant animals) before it was prescribed to women, and this case is the root of many countries’ animal testing safety laws today.
Thousands of mice and other small rodents are used in animal experiments every year

Thousands of mice and other small rodents are used in animal experiments
every year

Animal safety tests usually come at the end of a long process of safety data collection that may include testing the product ‘in vitro’ (i.e. in a test-tube) and using a computer program to simulate what might happen to the drug inside the body. The regulations on what safety data is required for a new product vary from country to country (and also from drug to drug), but most drug authorities require all three types of data - animal, in vitro and computer- generated - for trials to be allowed to continue.

All this means that at some point, all ‘antiretroviral’ (anti-AIDS) drugs will have been tested on animals for safety.

There is an argument however that animals are actually fairly poor substitutes for humans and that some compounds that may well cause no harm to a mouse, could kill a human being. This is particularly the case for drugs that interact with the complex human immune system, such as the anti-inflammatory drug that caused major organ failure in six men involved in a trial at Northwick Park Hospital in London, England in 2006. However, such occurrences are rare.
Efficacy trials

While all drugs and vaccines have to be tested on animals to establish their safety, testing them to establish their effectiveness is a different matter.

HIV is a retrovirus specific to humans (hence the name ‘Human Immunodeficiency Virus’), which means it is not naturally found in any other animal. Some African primates, such as chimpanzees and a few species of monkey, are naturally infected with SIV (Simian Immunodeficiency Virus), which is believed to be the virus from which HIV originated. Chimpanzees can also be artificially infected with HIV in a laboratory. However most monkeys and chimpanzees have very efficient immune responses to SIV (and HIV), and do not develop AIDS, even after many years of infection. This can make it very difficult to assess whether a drug or vaccine actually works, so primates are not used as widely as human substitutes as they once were.

This said, there is one primate still commonly used to conduct efficacy testing: the Rhesus macaque monkey. Because Rhesus macaques originate from Asia, rather than Africa, they have never been exposed to SIV, and thus have no natural immune responses to it. A Rhesus macaque that is infected with SIV will therefore develop AIDS type illnesses in a relatively short time 2.

For this reason (and because they are not an endangered species like some other Asian primates), macaques are often used in HIV research. A few HIV drugs, such as AZT and tenofovir (see our Introduction to Antiretroviral Treatment page for more information about these), have been tested on macaques for efficacy, though stricter rules on the use of primates in animal testing, and greater knowledge of HIV, mean that more modern antiretrovirals are generally only tested on animals for safety reasons.

Vaccine development on the other hand makes extensive use of primates. Because it could be seen as unethical to give a healthy human a vaccine, and then expose them to HIV to see if the vaccine works (if it doesn’t, they’ll end up with HIV), animals can be used as substitutes to establish whether a vaccine is effective or not. This method can also be used to test the usefulness of current AIDS drugs (such as tenofovir) in preventing HIV infection. Such work of course raises significant questions over whether it is any more ethical to give a monkey HIV than a human, when it too may become sick with AIDS and die.

A fundamental problem with using macaques in vaccine research has been that they have different immune systems to humans. This means they cannot be infected with HIV-1 (although they are susceptible to certain strains of HIV-2), however they can be infected with SIV, or an SIV-HIV combination (‘chimeric’ virus) known as SHIV. A drug or vaccine that is effective in Rhesus monkeys infected with SIV or SHIV may not therefore be effective in humans with HIV. Conversely, a drug or vaccine that may be effective in an HIV positive human may be dropped because it appears ineffective in animals. Scientists have now constructed a simian strain of HIV-1 that differs from the human virus by only one gene and mimics early HIV infection, however the infected macaques did not develop AIDS3. Further research on this genetically engineered virus is necessary, however if successful this may make testing vaccines in primates potentially more reliable.

Monkey research has yielded significant discoveries about HIV in recent years4, including major findings that have strengthened understanding of early SIV and HIV infection5.
General research

As well as the testing of new drugs and other products, animals may also be used for more general research that aims to gain a greater understanding of a disease. Rhesus macaques, chimpanzees and even cats (who can get Feline Immunodeficiency Virus) may be used as human substitutes to see how HIV-like viruses operate within the body.
Rhesus Macaques are commonly used in HIV research

Rhesus Macaques are commonly used in HIV research

They can also be used to study natural phenomena such as transmission or disease progression, and the effects of non-therapeutic substances on HIV.

One example would be a study carried out in Rhesus macaques in 2006 6. Scientists looking at the effects of alcohol on SIV found that feeding the monkeys large quantities of alcoholic beverages over a short space of time (effectively making them ‘binge’ drink) could significantly speed up the rate at which HIV progressed to AIDS. This may well lead to a greater emphasis on moderate drinking amongst HIV positive people, and a reassessment of safe levels of alcohol. However, whether the results of this experiment could have been recreated using methods that didn’t involve animals is open to debate.
Can animal testing be justified?

Animal testing is an extremely controversial and hotly debated area, and there are many groups around the world that are strongly opposed to animals being involved in any form of experiment, even if it involves simply keeping them in captivity. Equally, there are groups who say that there is no alternative to animal testing, and that animals have saved many human lives. Some of the scientific and moral arguments for and against animal testing include:

* FOR: Animal testing is justified because of the many human lives that it can save
* AGAINST: There is no firm evidence that animal testing has saved anyone’s life directly, particularly in the case of HIV – most drugs could probably have been developed without the use of animals.

* FOR: Humans are clearly unique amongst animals in our abilities and intellect. Animals do not experience pain and emotion in the same way that we do because they lack language and the power of abstract thought
* AGAINST: An animal’s life is equal to a human’s and we have no right to assume otherwise simply because animals cannot express their pain and suffering in words

* FOR: Animals are the best way to test vaccines, because it would be unethical to give a human a vaccine, and then to try to give them HIV to see if it works.
* AGAINST: It is no more ethical to give an animal a life-threatening illness than it is to give one to a human.

* FOR: SIV-infected chimps and Rhesus macaques are good substitutes for humans, and make drug and vaccine development far more simple
* AGAINST: Monkeys and chimpanzees do not have identical immune systems to humans, and may not respond to drugs or vaccines in the same way. Rhesus macaques also cannot be directly infected with HIV. No HIV vaccine has yet been developed, despite many years of animal involvement.

* FOR: Any differences between animal and human biology are generally known, and can be factored in to experiments
* AGAINST: This overlooks the effect that stress may have on the normal functioning of an animal’s body, which may in turn affect the results of the experiment

* FOR: Not testing new pharmaceutical products on animals is highly dangerous
* AGAINST: Animals are often poor substitutes for humans, and some compounds that may well cause no harm to an animal, could seriously harm a human being. Likewise, a drug that is toxic to the animal it is tested on, may have no toxicity, and even therapeutic benefits in humans.

* FOR: There are no viable alternatives to testing pharmaceutical products for safety on animals. Scientists already use in-vitro studies and computer models, and animal testing comes only after these tests have been performed. If a drug fails either test, it will not be given to animals anyway.
* AGAINST: Studies have suggested that ‘micro-dosing’ (where only a tiny amount of a product is given to a human through the skin) could be a new and very effective alternative to animal experiments 7. The recent news that scientists have grown a small piece of human liver tissue from stem cells could also mean that it may one day be possible to perform initial 'human' safety trials in a lab8.

* FOR: There are very strong laws in place to ensure that distress and pain in animals is kept to an absolute minimum
* AGAINST: Pain and suffering still occur, and simply being in captivity can cause great distress to an animal, just as it would to a human. Plus, animal testing facilities cannot be monitored at all times, so the sort of treatment animals receive on a daily basis can never truly be known.

* FOR: It is a legal requirement that drugs are tested on animals for safety in the majority of countries. Scientists have no choice in this matter.
* AGAINST: Perhaps if laws on the necessity for animal testing were relaxed, or animal safety-testing were banned, it would encourage scientists to develop other methods of testing toxicity that were equally effective. At the moment, they have no incentive to do so, so only a small handful of alternatives are being tested.

* FOR: No scientist wants to cause any more injury to an animal than is strictly necessary. Most scientists build up strong attachments to the animals they use in their experiments.
* AGAINST: This may be the case, but it is also very easy to become blasé about something that you do every day, and forget the pain and suffering your work is inflicting. Animals may well become little more than useful objects of study, rather than live creatures, and this can mean they are treated as disposable rather than indispensable.

What do HIV+ people think of animal testing?

Many HIV positive people condone, or remain neutral on animal testing because they are aware that the drugs they take to keep them alive have very likely been tested on animals at some point in the past.
Could human 'guinea pigs' be viable alternatives to real ones when testing new drugs?

Could human 'guinea pigs' be viable alternatives to real ones when testing new drugs?

In September 2005, six well-known AIDS organisations in the USA got together to form ‘Patient Advocates Against PETA’ (PAAP), a group that opposed the strong anti-animal testing stance of People for the Ethical Treatment of Animals (PETA) 9. Formed of ACT UP DC, ACT UP Southern California, AIDS Healthcare Foundation, AIDS/HIV Health Alternatives, AmASSI and the HIV Incarcerated Task Force, PAAP argued that PETA’s constant high-profile protests were hindering scientists in their search for effective HIV vaccines.

Their work was however opposed by a number of HIV positive individuals, who declared they were strongly opposed to animal testing, and did not condone PAAP’s actions. A consensus amongst HIV positive people themselves on the benefits of animal testing is obviously not very forthcoming.
What is the future for HIV and animal testing?

In recent years, scientists have begun to investigate the possibility of genetically altering the genes of some animals (particularly mice) to give them immune systems that more closely resemble a human’s, and are thus susceptible to HIV infection. Such small animal models could be useful, both for those developing new vaccines, and for those testing drugs for safety, but such work is strongly opposed by those who do not believe that genetically modifying animals is morally right or safe, as well as by those who oppose animal testing altogether.

Another alternative recently proposed is infecting ordinary mice with a chimeric form of HIV, similar to the 'SHIV' used to infect primates. This would allow efficacy trials of drugs and vaccines to be performed on small mammals, which could perhaps be combined with safety trials to reduce the time taken to reach regulatory approval. However, this would potentially increase rather than reduce the number of animals involved in clinical testing.10

Regulations on animal testing have been tightened considerably in recent years, and animals, particularly primates, are used in far fewer experiments than they once were. In most countries (particularly the UK, which has the tightest regulations on the use of animals for science) facilities where animals are held are inspected regularly to ensure that animals are being kept in hygienic, safe and comfortable conditions.

Nonetheless, animal testing is still very strongly opposed by many groups who believe that any form of animal exploitation is wrong. The majority of anti-vivisection groups stage peaceful protests that aim to raise awareness of the harm and pain that animal testing can inflict, and raise support amongst the public for a ban on the practice. However a small minority of animal rights activists have resorted to more extreme tactics, which have included intimidation of those directly involved in experimentation, intimidation of their families, suppliers and business partners, and criminal acts, ranging from harassment and vandalism to blackmail and arson 11, 12, 13.

Unfortunately, while such groups receive substantial media coverage, their extreme actions tend to drown out the messages of more moderate groups, who are simply calling for a reassessment of the law, or greater research and assessment of alternative methods. Their behaviour creates a counter-productive situation, whereby those who conduct experiments on animals become more determined to continue with their work because of the opposition they face, and the government refuses to launch a proper investigation into the current laws in case they are seen as ‘giving in’ to extremists. It also risks portraying all animal rights campaigners as extreme activists and all scientists as cruel animal abusers.

In reality, views on animal testing are not nearly as polarised as this. There are many moderate anti-vivisection groups, just as there are many scientists who would prefer not to test on animals if they had a choice. A meaningful debate between the two may well help to further progress into ending the reliance on animals for safety and efficacy testing, but while the issue remains connected to such controversy and extremism, discussions of this kind seem to be few and far between.

It may be that one day animal research produces a vaccine or a cure for HIV that saves millions of human lives. If this is the case, then some justification can perhaps be found in using animals for our own purposes. Until this time however, anti-vivisectionists need to remain focused on finding alternatives, informing and changing legislation and keeping testing on animals to an absolute minimum. It is only through such positive action that true progress can be made.
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Written by Bonita de Boer
References:

1. UK Medicines Act, 1968
2. NIAID Division of AIDS "Animal Models"
3. Theodora Hatziioannou et al. (2009) 'A Macaque model of HIV-1 Infection' PNAS
4. Lackner, A.A & Veasey, R.S (2007) 'Current concepts in AIDS pathogenesis: insights from the SIV/macaque model', Annual Review of Medicine, 58:461-76
5. Veazey, R.S et al (1998) 'Gastrointestinal tract as a major site of CD4+ cell depletion and viral replication in SIV infection', Science Vol.280; 427-431
6. "Chronic Binge Ethanol Consumption Accelerates Progression of Simian Immunodeficiency Virus Disease" Alcoholism: Clinical and Experimental research, October 2006, Vol. 30 Issue 10.
7. "'Safer' drug test technique hope" BBC.co.uk, 08th October 2006
8. "Liver cells grown from cord blood" BBC.co.uk, 31st October 2006
9. "AIDS Coalition Clashes with Animal Rights Activists" The New Standard, 20 September 2006
10. HADAS, Eran et al. 11 May 2007, 'Testing antiretroviral drug efficacy in conventional mice infected with chimeric HIV-1', AIDS, Vol. 21 No. 8.
11. "Man admits animal rights bombs" BBC.co.uk, 17 August 2006
12. "Four jailed in grave-theft case" BBC.co.uk, 11 May 2006
13. "3 animal-rights activists get prison time" San Francisco Chronicle, 13 September 2006

Last updated December 23, 2009
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