2.  Area of science devoted to the study of the processes of life, the prevention and treatment of disease, and the genetic, lifestyle and environmental factors related to disease and health.  Divided into 3 broad categories:  Basic  Applied  clinical

3.  What do you think of first?  A “mad” scientist performing experiments in a jam- packed laboratory?  Dr Frankenstein?  White mice?  All sorts of potions boiling under Bunsen burners?  White lab coats?  Animal testing?  Maybe ----- maybe not

4.  Basic research is done to increase the fundamental knowledge and BASIC understanding of physical, chemical and functional mechanisms of life processes and diseases  It is not directed toward a solution  Often involves describing, measuring and manipulating natural systems  Building blocks  Difficult because it doesn’t look for a solution – it’s just trying to EXPLAIN things  Often, a researcher will contribute findings that are valuable to other studies

5.  Directed toward specific objectives, such as the development of new drugs, treatments or surgical procedures  Application of existing knowledge (quite often obtained from basic research) to a specific biomedical problem  Conducted with animals, non-animal methods like computer models or tissues, and with humans  Examples of applied research  New anti-cancer drugs  Studies of human growth factors  Production of monoclonal antibodies for use in the diagnosis and treatment of cancer

6.  Involves testing potential drugs and treatment in humans  Not always the end result – can lead scientist to go back to the lab for improvements, changes, or a new beginning  Clinical research has a direct relationship to prevention, diagnosis, or treatment of a specific disease  Areas of study:  Human clinical trials  Psycho-social  Disease control research  Behavioral

7.  Pap smear – Dr. George Papanicolaou showed that a sampling of cells from a woman’s cervix could detect early stages of cancer ---------there has been a 70% reduction in the number of deaths from cervical cancer  Smoking – research shows that smoking and lung cancer are directly linked and that smokers die more often from a heart attack than non-smoking persons

8.  chemical, mechanical, mathematical and computer simulations – used in preliminary stages  In vitro tests – use of tissues or cells – early and intermediate stages  Non-human animal trials – provide reliable and complete data on how a living system functions – offer very good indicator of how humans will react to a new drug or medical procedure  Human studies – carefully staged using human volunteers – involves taking laboratory data on the safety and effectiveness of new meds  Epidemiological studies – another type of human study – look at occurrence and distribution of disease in a population

9.  Chemical testing can detect a substance or measure potency of certain substances and help develop vaccines, drugs and vitamins  Ex. When studying the botulism toxin and its binding with its antibodies, traditional, older methods would have required the use of thousands of mice (sacrificing). Now, one rabbit can produce enough antibodies in a month to perform the same tests that would have been done on the mice

10.  Because of advances in computer technology, scientists can predict biological responses based on chemical structure and activity within an organism.  Large data bases can be maintained for future comparisons of new compounds to previous ones  Researchers are using this approach in the fight against HIV/AIDS and in the development of new and improved medications  New data is being used to compare HIV compounds with SIV (simian immunodeficiency virus – found in monkeys)

11.  Computer models increase the efficiency and speed of research  Reduce the number of animals needed for research  Computers do not generate data – they only process the data  Rely on existing information  Sophisticated computer equipment and software are often prohibitively expensive

12.  In vitro means “in glass” – scientists use the term to describe any biological process or reaction that takes place in an artificial environment  Cells or tissues used in in vitro studies come from a living organism – plants, humans, animals  Examples of in vitro studies:  Ames test for mutagenicity – compound is tested for its ability to cause mutations - signaling that it could cause cancer – not entirely conclusive because not all mutations cause cancer – more research being done  Pregnancy tests – rabbit test – now have at home tests which are convenient and do not involve animals

13.  Single effect studies of a substance in isolation  Less expensive  Requires less time  Offers more control than testing in animal subjects  Very difficult to put the multi-step process of cancer together in vitro  Cells grown in a culture medium do not act as they would in a living organism – no blood supply, oxygen, nervous system and glandular function  Tissues in vitro tend to forget how they are supposed to act  Data may not be 100% reliable

14.  Not feasible to conduct all research experiments on humans – ethical reasons and feasibility  Animals offer a very reasonable look at how humans will react to certain compounds, procedures, or treatments  They are a living system – rather than a non- living system like in vitro

15.  Ethical alternative to the use of humans  Whole, integrated, biological system  Structure and function of animal cells, tissues, organs, etc. behave in much the same way as humans  Not totally IDENTICAL to humans  Because of this, there are more variables that have to be introduced

16.  Most often used in the development of prescription drugs  Two key questions have to be answered after extensive lab testing, animal research and testing:  Is the drug biologically active in humans  Is it safe in humans  Three major phases of clinical trials after a pharmaceutical company files an IND (investigational new drug) application with the FDA

17.  Phase I  Determine a drug’s interaction with the human system  How the drug is absorbed, distributed, metabolized and excreted  Small number of healthy volunteers  Takes about 1 year

18.  Phase II  Use controlled tests that help determine a drug’s effectiveness  100-300 volunteers  Simultaneous animal and human tests to continue to test the safety of the drug  Takes about 2 years

19.  Phase III  Confirmation of earlier results  Identify adverse events  Involves 1000 – 3000 volunteers in hospitals or medical clinics  Takes about 3 years

20.  Upon completion of the human trials, the pharmaceutical company files a NDA (new drug application) with the FDA  Comprehensive statement is provided based on the:  Drug structure  Scientific rationale  Purposed of the drug  Pre-clinical animal trials  Lab study results  Human clinical testing results  Drug formulation  Production details  Proposed labeling  Takes about 2.5 years to complete

21.  Currently takes about 12 years from the initiation of testing until FDA approval  Cost is hundreds of millions of dollars

22.  Study of disease incidence and its distribution in a population  Need to know how diseases are caused  Three general types  Experimental – human equivalent to animal testing – ethical and legal considerations  Descriptive – analyze data on distribution of disease – often done in conjunction with other countries  Observational – data is taken from individuals or small groups – to note how particular variables

23.  One of the first epidemiological studies may have been in England in 1775 when the incidence of scrotal cancer was first noticed in chimney sweeps  Early 20 th century – studies showed that the Black Plague during the 14 th century was spread by fleas on rats to humans  Cholera outbreak from contaminated water in 1854  Legionnaire’s Disease outbreak in 1976 traced to bacterium in static water supplies  Smoking study in 1952 linked smoking to lung cancer

24.  Useful in identifying patterns in disease or injury  Offer a direct opportunity to study the effects of exposure to chemicals and disease-causing agents on humans  Considerable human exposure can take place before a toxic effect is noted  Difficult to find a direct cause and effect relationship  Methodologies are limited  Expensive  Difficult to find “control” groups – people who have not been exposed to the causative agent

25.  Vaccines  New therapeutic drugs  Diagnostic tools  Workplace safety  Quality of life

26.  So what’s the big deal? What’s so special about research? It’s boring…………………….. This unit is boring…………………….. Or is it??????  Without research:  There would be no cardiac surgery – no DaVinci system  No heart-lung machine  None of the 600,000+ cardiac surgeries per year would be performed  Treatment for cancer would be still in the “dark ages”  There would have been no discovery of p53 or tumor suppressor genes

27.  No insulin pumps  No realization that exercise helps make diabetics healthier  There would be no improvement of oral diabetic medications to get people off 4-5 injections per day.  Bone marrow transplants would not be performed  Stem cell transplants would not be possible  Vaccinations for deadly diseases would not be available – smallpox, polio, tetanus, diphtheria, chicken pox, Hepatitis A and B,  Fluoride treatments would not be possible  No antibiotics

28.  Anthrax  Cholera  Diphtheria  Hemophilus B  Hepatitis A  Hepatitis B  Influenza  Measles  Meningococcal Meningitis  Mumps  Pneumococcal

29.  Virus attacked the spinal cord, destroying nerve cells crucial for muscle movement  Was not identified as a contagious disease until the mid-20 th century.  Albert Sabin developed the vaccine that could be given orally and made from a live virus. The reason for this is to intruduce into the body, stimulating and immune response.

30.  Appeared in the early 1980’s  Rate of new infection is about 40,000 people per year  Transferred from person to person as an INTRACELLULAR virus – becomes part of the cell’s DNA  May remain dormant in the person’s lymph system for 10-12 years – continues to multiply and shed itself in bodily fluids  If the immune system becomes impaired, the HIV infection progresses to AIDS  Opportunistic infections take place as well as some cancers  Animal research has played an important part in how much we now know about AIDS

31.  HIV is a retrovirus meaning that the virus uses specific enzymes within the cells to survive  Treatment is directed toward the use of antiretroviral drugs  HIV needs an enzyme called transcriptase to replicate – older drugs target this enzyme  Now, we know that HIV also uses protease to replicate  Protease inhibitors now being developed for improved treatment  Treatment with a triple-drug therapy called HAART (highly active antiretroviral therapy) helped reduce deaths by 42% during the mid 90’s

32.  Tremendous amount of work being directed toward the development of vaccines  Biggest challenge for the researcher is the fact that HIV mutates easily  Use common sense to prevent spread