Keywords Health & Medicine

Since this early success, the knowledge of viral structure and mechanism of action has advanced greatly. Until the development of tissue culture, however, there was no way of growing viruses in the laboratory. Although some cells had been grown in culture before 1945, the principal breakthrough occurred when Dr Raymond Parker at the then Connaught Medical Research Laboratories in Toronto defined a chemical-nutrient medium in which cells would grow and replicate.

Parker's discovery permitted Jonas Salk to develop his polio vaccine. Much of the Salk vaccine was produced in Toronto for field trial in Canada and the US. The virus was grown in monkey kidney cells, separated from the cells, concentrated and then killed with formalin. The success of the new killed-virus vaccine was soon apparent and the annual polio epidemics disappeared. The Sabin polio vaccine, prepared from a weakened or attenuated virus also grown in monkey kidney cells and given orally, was developed a few years later.

More recently, human diploid fibroblast cells (which, in the body, develop into connective tissue) have been grown in culture. These cells have been more rigorously defined than kidney cells isolated from monkeys and have permitted the preparation of more highly purified viral vaccines (eg, Salk and Sabin polio, rabies, measles, mumps, rubella, hepatitis A). The first killed-rabies vaccines made by Pasteur were prepared in neural tissues (eg, mouse brain or spinal cord) and later in duck embryo cells. The injections were painful and multiple doses were required. With the diploid-cell-grown vaccine, fewer doses are required and adverse reactions are much reduced. The vaccine may be given either prophylactically or after exposure.

Other attenuated viral vaccines in use include the veterinary strain of rabies (known as the ERA strain), developed at Connaught but now part of SANOFI PASTEUR LIMITED, and the measles and rubella strains currently being widely used. Future viral vaccines will be of several types: traditional whole virus vaccines, extensively purified from defined cell substrates; split or single-antigen vaccines, prepared by extraction, chemical synthesis or GENETIC ENGINEERING (eg, those for foot and mouth disease); and DNA vaccines, where DNA coding of the disease antigen is injected into the body which then produces a vaccine created by the body's own immune system cells.

Viral vaccines have developed in recent years to treat and prevent a number of diseases. These vaccines include those engineered for RNA viruses, rotavirus, INFLUENZA A and B, human papilloma virus (HPV), and varicella-zoster virus (shingles). Researchers anticipate the development of vaccines for human immunodeficiency virus (HIV) and hepatitis C through the use of biological products in the future.

Bacterial Vaccines
Bacterial vaccines are of 3 basic types: killed whole organisms or bacterins, including those for pertussis (whooping cough) and those for use in the veterinary or aquaculture fields; single-antigen vaccines extracted from bacteria or prepared by genetic engineering; and toxoids. Many bacteria, such as those that cause tetanus, pertussis or diphtheria, release toxins that cause cellular damage. These toxins have been purified and inactivated, usually with chemicals to produce toxoids. When injected, toxoids induce the formation of antibodies against the original toxin.

Some other bacterial vaccines produced include typhus, typhoid, cholera, haemophilus, influenzae type B, pneumococcus, meningococcus and bacille Calmette-Guérin (BCG, used for the prevention of tuberculosis). Vaccines for veterinary use include those for household pets, farm animals and other cultivated species, such as mink or fish. The vaccination of fish is a new approach necessitated by the crowding of fingerlings in AQUACULTURE operations. Administered by injection, immersion or spray, such vaccines are remarkably effective.

Canadian researchers are examining the potential for a new vaccine for bacterial meningitis. The current vaccine is only effective against certain types of meningitis, and there is a need for a broad spectrum vaccine. The biology of the meningitis bacteria have made it very difficult to develop a broad spectrum vaccine because there are no animals that respond to the bacteria in the same way as humans, and the infection is too dangerous to risk testing a vaccine on human subjects. However, Canadian researchers have developed a unique animal mouse model that has been genetically engineered to produce the necessary human cells. This mouse model opens the door to the development of a broad spectrum meningitis vaccine.

Blood Fractions and Serums
Beginning in the 1930s and stimulated by WWII, blood serum (the fluid that remains after blood is clotted) was collected and freeze-dried. When reconstituted with water, this product was of some use in the treatment of blood loss and shock resulting from trauma. Methods of separating blood plasma (noncellular fluid) into its constituent proteins were developed in the US. These permitted the Canadian Red Cross Blood Transfusion Service to expand the applications for donated blood. Products prepared from donated blood include red cells, white cells, platelets, and plasma which is fractionated to albumin, immune serum globulins (including specialized products such as tetanus, Rh and rabies immunoglobulins), and coagulation factor concentrates for the treatment of hemophilias A and B. Canadian plasma was fractionated at Connaught between 1953 and 1987. Since then, all Canadian plasma has been processed under contract by commercial fractioners in the US. Hemosol BioPharma Inc, a Toronto biotechnology company, develops blood-protein based products, which avoids the potential risks associated with blood.

Hormones Until the late 1980s, Canada produced INSULIN from bovine and porcine pancreas. Insulin was first isolated in Toronto by Frederick G. BANTING and Charles H. BEST in 1921-22. The human form of this protein is now manufactured outside Canada using genetic engineering.

Monoclonal Antibodies
Monoclonal antibodies are used to treat a variety of diseases caused by cancer cells, infectious agents or toxic inflammatory substances. These antibodies are produced in laboratories in a cell culture to create multiple identical forms of the same cell. This results in very pure antibodies that act against specific antigens. Canada is involved in research to produce antibodies targeted at prion-related diseases that cause severe damage to brain cells in humans and animals, such as transmissible spongiform encephalopathy, Creutzfeldt-Jakob disease and chronic wasting disease.

Biological products offer the hope of treatments for many debilitating diseases. The future of medicine may well involve the ability of researchers to investigate new treatments derived from these products. However, MEDICAL RESEARCH does not exist in a vacuum. The division between medical research and social convention can cause debate about the appropriateness of a given medication or vaccine. The controversy over vaccinating young women against human papilloma virus (HPV) before sexual maturity is one example. While this vaccine offers the hope of preventing the development of cervical cancer in generations of women, the vaccine is delivered within the context of social expectations of proper female behaviour.

See also ESTROGEN.

Author A.A. MAGNIN Revised: PATRICIA BAILEY

Links to Other Sites
Canadian Blood Services
Canadian Blood Services is a not-for-profit, charitable organization whose sole mission is to manage the blood and blood products supply for Canadians.

Héma-Québec
Learn about compatibilities of various human blood types and other blood facts at the Héma-Québec website.

Centre-INRS-Institut Armand-Frappier
The website for the INRS-Institut Armand-Frappier research centre, a leading-edge health-related research organization in Québec. Check out “Research Areas” for an overview of the Centre’s multidisciplinary programs and facilities, profiles of key personnel, and opportunities for graduate study. See also the “Canadian Irradiation Centre” and the link to colourful online exhibits at the “Armand-Frappier Museum.”

Sanofi Pasteur
The website for Sanofi Pasteur, the vaccines division of sanofi-aventis Group. In the upper menu, click on "Sanofi Pasteur in Canada" for a brief history of Connaught Laboratories and a profile of founder Dr. John G. FitzGerald.

TMX Group
The online home of TMX Group, which owns and operates the Toronto Stock Exchange and the TSX Venture Exchange. For real-time and historical market data, sector profiles, and financial information about listed companies, click on listed company directory on left side of page or enter stock symbol in the search box.

Tainted blood scandal
A detailed CBC report about the Krever Inquiry, an investigation of "all activities of the blood system in Canada, including the events surrounding the contamination of the blood system in Canada in the early 1980s."

Sanofi-Aventis BioTalent Challenge
The website for the Sanofi-Aventis BioTalent Challenge, described as annual student science competitions. Check out the section "Students & Teachers" for background information about biotechnology, online games, and more.