4th National Symposium on Biosafety

Research with Nonhuman Primates

Peter Gerone, PhD
Tulane Regional Primate Research Center
Tulane University Medical Center
18703 Three Rivers Road
Covington, LA 70433
504-892-2040

The use of nonhuman primates in biomedical research has been very important in expanding our knowledge about human disease and behavior. They have been used in a wide variety of studies including infectious and metabolic diseases, physiology, pharmacology, toxicology, and behavior. As is often the case, the opportunities to gain knowledge also come with some risks and using nonhuman primates in the laboratory is no exception. Depending on your perspective that risk can either be small or large. What I mean is that if we look retrospectively on what has happened in the nonhuman primate laboratory the record is really pretty good. We've had very few instances of adverse affects mostly from infections and even in those instances the disease was limited to a small number of people and certainly it never got out into the community to any large extent. So from that point of view the risk is small. I often tell the people who work at our primate center that probably the biggest risk they take is driving their cars to work in the morning.

On the other hand, if you contract an infection such as monkey B virus and its fatal, you can hardly dismiss that as a small risk. The second perspective is to look at it from the point of view of the potential that's there. And the potential indeed is great. I don't have to review for you what Dr. C.J. Peters told us about the opportunities for introducing new agents in the human population by way of monkeys or travellers who arrive from various parts of the world. That is a very, very serious concern.

I think the Ebola Reston experience taught us a lot of things. It taught us for one thing that it is possible to bring in a human infectious agent by that route. Fortunately this virus wasn't very pathogenic for humans. It also taught us that its very difficult to predict where an agent may come from. I remind you that all of the Ebola experiences we've had in humans have been limited to the continent of Africa, yet the Reston monkeys came from the Philippines. One would not have expected an Ebola virus to come from that direction. Another thing that we've learned is that we cannot predict mortality in one species on the basis of what it might be in another species. We all know about the B virus experience where in the monkey it's rarely a fatal disease unless the monkey is immunosuppressed. However in man its almost always fatal.

We see the same thing with the simian immunodeficiency virus. In the natural host, the African species, the virus does not cause disease, but if you take that virus and put it into the Asian species then you do cause an immunodeficiency.

In thinking about the potential for introducing new viruses to the human population, one shudders to think about what the world reaction would have been had the epidemic of human AIDS been traced to monkeys that were used in the laboratory. I'm sure that would have drastically affected the future of primate research!

Of course, we all worked with African monkeys before we knew they were infected with the SIV. They were used for many years and often without the protection that we now use whenever we work with simian immunodeficiency virus.It is clear that, if the primates had carried a virus that was pathogenic for humans, there were plenty of opportunities for crossing over.

How are primates different from some of the animals that Dr. Fox talked about? Well there are several things that I can think of. One is that they have more strength, so you have to take that into account from a safety point of view. One thing that people who are not used to working with monkeys rarely think about is the fact that a monkey can reach out and grasp which is something most other laboratory animals cannot do. They are certainly more intelligent, so if there's a way of getting loose and getting at you they will figure it out. Because of their close relationship to humans, they are more likely to bring in zoonotic diseases

This is a photo that illustrates that a monkey can extend his entire arm beyond the bars of the cage. If you're walking by and you happen to be wearing earrings or jewelry of some sort or have long hair, those can all be targets for the monkey with serious consequences for the worker.

Actually, when you think about the biosafety of working with nonhuman primates, it starts before you even get the primates to the laboratory. The areas of concern include buying and shipping them, quarantine, breeding and holding, experimental use, and finally the disposal.

One has to consider the safety factors related to the species. Some monkeys are bigger than others. There's a vast difference between handling a squirrel monkey and handling a baboon. Some monkeys are far more aggressive by their very nature than other species. The incidence of zoonotic diseases can vary by the species of monkey. Generally speaking those that come from the New World monkeys, Central and South America have less zoonotic diseases than those that come from Asia and Africa.

When you procure or ship animals you have to think about the source and how are you going to ship them and handle the shipment safely. The safest monkeys are those that come from SPF colonies and then in descending order of safety would be domestic colonies, foreign colonies, and wild caught. Those that are brought in from foreign countries come in contact with a lot of people before they get to your laboratory giving them more opportunities to pick up diseases like hepatitis and TB. Importation statistics show that we are using fewer wild caught animals in the United States so that's going to become somewhat less of a problem.

Shipping is usually by air or truck. By air if it's international; by truck if it's domestic. If you'r an importer, you now have the responsibility for decontaminating the airplane. If you get them by truck you must decontaminate the truck.

Once the animals arrive in the laboratory we think of two types of hazards, the infectious hazard and the traumatic hazard. In terms of the infections, which are our main concern, you have the natural infections that the monkeys bring to the laboratory even though they may have picked them up from people while en route to the laboratory and then you have the experimental infections. All evidence supports the fact that the ones you have to worry about most are the natural infections. Rarely have we had any instances of individuals being infected with the agents with which they're working in nonhuman primates. Its always the ones that you don't know about that come in naturally with the monkeys.

The routes of infections you have to worry can be by aerosol (TB), puncture wounds (rabies or B virus), or ingestion (salmonella, shigella and the parasites). The primate zoonoses that are of special concern include B virus, tuberculosis, hepatitis, the enteric bacteria, and parasites. The B virus is the one we worry the most about. In our laboratory we have bite kits that are available anywhere where we work with the monkeys. The kit is a plastic box that contains all of the materials including instructions, scrub brushes, detergents, betadyne, and the culture swabs. Those bitten or scratched must scrub with the detergent and bleach for five minutes by the clock. Then for ten minutes they scrub with betadyne. Swabs are taken from the monkey's mouth and a serum sample is drawn. The injured employee then goes to our clinical laboratory where a blood sample is taken as reference serum. Each incident is reported in a "Bite and Scratch Log".

The trauma include bites & scratches, trips & falls, equipment related injuries and chemical exposures. One of the most important measures for the safe use of nonhuman primates is proper restraint, either in the way of chemical(anesthesia) or physical methods. The best and safest way is with chemical restraint. There are several types of physical restraint. Tying down the animal or having manual assistance to hold and immobilize the animal properly are the most common methods. The primate chair is useful if you must do repeated procedures on the animal, and the pole and collar are less frequently used methods. A pole and collar is often used to get a conscious monkey to the primate chair.

Another method that we rarely think about in terms of working safely with animals is to train them. If you have a procedure that's going to require repeated practices on the same animal, the time necessary to train the animals may pay big dividends for long term studies. The result is that you save labor, it is safer, and the procedures are less stressful for the animal. Most investigators are surprised at how trainable the monkey can be.

The one piece of equipment that has done the most for the safe handling of monkeys is the squeeze back cage. Those cages have taken much of the risk away from doing experimental procedures on monkeys. They are commonly used in most laboratories where research is done with nonhuman primates.

Personnel protection include the caps, the gowns, the masks, the face shields, gloves, and foot covers. It is good practice to require the wearing of at least a minimum of protective clothing when workers are in contact with any monkey, whether or not it is experimentally infected.

In conclusion, we can say that the potential for serious zoonoses from primates definitely does exist. That's something we must expect but the good news is that we have the technology and know-how to work safely with nonhuman primates in the laboratory.

Office of Health and Safety, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Mail Stop F05 Atlanta, Georgia 30333, USA Last Modified: 1/2/97
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Research with Nonhuman Primates