Problem-based learning (PBL), as a method of instruction, took root at McMaster University's Medical School in the late 1960s. Today it is used by 22 medical schools in North America as well as Australia, Israel, and the Netherlands (Mayo, Donnelly, and Schwartz, 1995). An extensive review of its strengths and weaknesses has been written by Albanese and Mitchell (1993). Its use in basic science programs is just beginning and is spearheaded by the University of Delaware, which just recently held its 5th annual international conference. An example of its use in a physics course was published by Duch (1996).

PBL has been used and defined in various ways (e.g., Barrows, 1986), but here I stay with the classical method: Small groups of students (perhaps 4-8) meet with a tutor (facilitator) to solve real world problems (written case scenario, research papers, video clip, novel, etc.). Together they try to identify the broad nature of the problem - the issues and the learning objectives. They define what they know and what they need to find out. Students divide up the study tasks and adjourn the meeting to dig into the literature. At a second meeting the students share their results and try and resolve the basic problems they identified earlier. At this point, the tutor may provide additional information (e.g., new lab tests, experiments, observations, complications, research papers). Again, the students refine the problem into things they know and need to know, subdivide the workload and adjourn. At a third meeting their information is pooled and a report written. Often in this session, the group becomes introspective about their various problem-solving strategies with the hope that they will improve with later cases.

There is rich literature about PBL and the various skills that are needed to be successful. What is missing are the PBL problems. The literature holds few case examples that can be passed along to other instructors (e.g., an exception being Rangachari's, 1991, article on PBL in an undergraduate course in pharmacology). We are a long way from achieving the bank of cases developed for business at places like Harvard. Hence, every case helps. Below I give a PBL case approach using the controversy over HIV and AIDS.

The topic of acquired immunodeficiency syndrome, AIDS, is ideal for case study teaching. The topic is complex, important, controversial, and has public policy implications. It is of vital interest, and in every course where I have used case studies, those cases involved with AIDS always receive the highest marks from students.

Over the past ten years, the scientific community has been alternately challenged, irritated, frustrated and bemused by Dr. Peter Duesberg of the University of California at Berkeley, and his position on AIDS. Duesberg, a renowned virologist and a member of the prestigious National Academy of Science, does not believe that HIV causes AIDS. Rather, he claims that AIDS is the result of recreational and anti-HIV drugs. Virtually all scientists who have studied the issue believe Duesberg's opinions to be extreme, although some maintain that HIV is not the sole cause of AIDS. A December 9, 1995, issue of Science devoted an eight page special report on "The Duesberg Phenomenon." Nevertheless, Duesberg believes his views have not received the attention they deserve and his research program has been seriously affected because of his unpopular position. He has not received any grant support since becoming embroiled in the controversy according to reports in The Scientist (March 20, 1995). In that publication, he is quoted in explaining why the AIDS community has rejected his views and why he can't get funded for research:

"A whole generation of AIDS scientists, retrovirologists - in the last 10 years their names, their papers, not to mention their fortunes, solely and exclusively rest on one thing, on HIV. If HIV is not what it is said to be...all these people...would be nobody.... In fact, worse than that: Many would be rightfully blamed for having intoxicated 200,000 Americans with AZT every six hours and panicked millions of people with a positive AIDS test...They would have done unbelievable harm in the name of this hypothesis if this hypothesis were proven wrong. So these people cannot afford in the least bit to consider an alternative that might end their careers."

Student Assignment

The following assignment is basically that used by practitioners of problem-based learning. As I have outlined above, the case requires part of three class periods. It involves the use of papers from the literature rather than a written scenario. I have used it for groups of 3-6 students working in permanent groups without tutors with reasonable success. Basically, I give the groups sets of papers and ask them to identify the learning issues and to educate themselves about AIDS.

I give out two 1988 Science magazine articles: a short critique by Duesberg entitled "HIV is Not the Cause of AIDS," and an adjoining article: "HIV Causes AIDS," by noted experts Drs. W. Blattner, R.C. Gallo, and H.M. Temin. I also include copies of their rebuttals to one another.

On Day One, the students' basic task is to identify the issues that are important in the papers, as well as to identify the terms, concepts, and information they need in order to resolve the problem as they see it. Then the students subdivide the workload, and after class go to the library, the Internet, and their texts to try and resolve their questions.

On Day Two of this case, the students pool their information and summarize their knowledge. To aid the process, I give them a couple of additional papers to be sure that certain points are addressed. For example, Duesberg's (1991) article highlights his views especially well. Also, Moore's (1996) review of Duesberg's book "Inventing the AIDS Virus" is useful, as is the Scientific American (1995) article on "How HIV Defeats the Immune System" by Nowak and McMichael.

With these papers in hand, the students are asked to again identify any new issues, terms, and information they need. Once again they set out and collect the information for the next class.

On Day Three of the case, the students pool their information for the last time and prepare to deal with the final assignment. In their groups I ask them to evaluate the nine points that Duesberg made in his original Science article where he claimed "HIV is not the cause of AIDS because it fails to meet the postulates of Koch and Henle, as well as six cardinal rules of virology." In class, the groups write brief summaries about each of the nine points in light of our most recent information.

Below I show one student group's paper. Although not ideal, it gives an idea of what can be accomplished in an introductory biology course.

References

• Albanese, M. and S. Mitchell. 1993. Problem-based learning: A review of literature on its outcomes and implementation issues. Academic Medicine 68: 52-81.
• Barrows, B.J. 1986. A taxonomy of problem-based learning methods. Medical Education 20: 481-486.
• Blattner, W., R.C. Gallo, and H.M. Temin. 1988. HIV causes AIDS. Science 241: 515.
• Blattner, W., R.C. Gallo, and H.M. Temin. 1988. Blattner and colleagues respond to Duesberg. Science 241: 514 & 517.
• Duch, B.J. 1996. Problem-based learning in physics: The power of students teaching students. Journal of College Science Teaching, March/April 1996: 326-329.
• Duesberg, P. 1988. HIV is not the cause of AIDS. Science 241:514.
• Duesberg, P. 1988. Duesberg's response to Blattner and colleagues. Science 241: 515-516.
• Duesberg, P. 1991. AIDS epidemiology: Inconsistencies with human immunodeficiency virus and with infectious disease. Proceedings of the National Academy of Science 88: 1575-1579.
• Goodman, B. 1995. A controversy that will not die: The role of HIV in causing AIDS. The Scientist 9(6): 1 & 6-7.
• Mayo, W.P., M.B. Donnelly, and R.W. Schwartz. 1995. Characteristics of the ideal problem-based learning tutor in clinical medicine. Evaluation and the Health Professions 18: 124-136.
• Moore, J. 1996. A Duesberg adieu! Nature 380: 293-294.
• Nowak, M.A. and A.J. McMichael. 1995. How HIV defeats the immune system. Scientific American Aug. 1995: 58-65.
• Rangachari, P.K. 1991. Design of a problem-based undergraduate course in pharmacology: Implications for the teaching of physiology. American Journal of Physiology 260(6): Supplement: S14-S21.

Student Response to Duesberg

Duesberg's theory contains nine parts saying that HIV is a harmless retrovirus that may serve as a marker for people in AIDS high-risk groups. AIDS is not a contagious syndrome caused by one conventional virus or microbe. AIDS is probably caused by conventional pathogenic factors: administration of blood transfusions of drugs, promiscuous male homosexual activity associated with drugs, acute parasitic infections, and malnutrition. Drugs such as AZT promote AIDS, rather than fight it. In our opinion Duesberg is a biological flake.

Duesberg's first three parts to his theory rely on Koch's 1st, 2nd, 3rd postulates: (1) free virus is not detectable in most cases of AIDS; (2) virus can only be isolated by reactivating virus in vitro from a few latently infected lymphocytes among millions of uninfected ones; (3) pure HIV does not cause AIDS upon experimental infection of chimpanzees or accidental infection of healthy humans.³ First, we know Koch's postulates are more of historical interest than practical use. We know for a fact that people who receive HIV tainted blood become HIV+ and come down with AIDS. People who receive HIV-free blood don't get AIDS (unless they get HIV somewhere else). Thus, it is the HIV, not the transfusion, that causes AIDS. As far as HIV not being able to be isolated in 20-50% AIDS cases as Duesberg points out, we know that with a few recent exceptions, everyone with an AIDS-like immune deficiency tests positive for HIV. Everyone with HIV apparently gets AIDS eventually, after an average of 8 years. (There may be some exceptions for people having natural immunity.) In summary with his first three parts to his theory, Duesberg is trying to fit a new virus into old postulates.

In his fourth part, Duesberg is claiming HIV doesn't kill enough T-cells to cause AIDS.¹ This can be proven wrong with the definition of apoptosis, which is a natural suicide mechanism by which the body takes care of extensively damaged cells, especially when their chromosomal DNA is damaged or cleaved. Apoptosis in mature T-cells has been proposed to be induced in at least two prominent ways by HIV. The first involves signals generated upon binding of HIV surface proteins to CD4 of activated T-cells. This can not only occur upon binding of HIV itself to the T-cells, but also upon binding of infected T-cells, having viral protein gp120 on their surface, to uninfected cells. The second mechanism involves modification of accessory-cell functions by HIV, changing the balance of activation signals required to prevent apoptosis in the mature T-cells. This can be accomplished either by enhancing the amount of apoptic signals or reducing the amount of balancing preventive signals.²

In his fifth part to his theory, Duesberg says that HIV remains inactive during AIDS and therefore it can't be the cause. What Duesberg could not have known in the 80's is that the common cause of AIDS is due to the fact that opportunistic infections generally happen because of a dysfunctional immune system, and the cause of this disjunction is HIV infection.⁴ Of course, there can be other causes - genetic or environmental - but rarely is the dysfunction as devastating as that found in the later stages of HIV infection, and never is it as common.

In his sixth part to his theory, Duesberg is saying that the 8-year period between the onset of antiviral immunity and AIDS is unusual, and that AIDS should occur early when HIV is active. What Duesberg has to realize is that AIDS occurs after the immune system has been broken down. HIV causes this breakdown by depleting the T-cells of the immune system and this process takes a long time because as Duesberg points out in his fourth part of his theory - the body is very good at regenerating T-cells to compensate losses to HIV.

In his seventh part of his theory, Duesberg points out that retroviruses are not cytocidal and, on the contrary, they often promote cell growth.¹ We now know that retroviruses are divided into 3 categories, two of which fit Duesberg's description (oncoviruses and spumaviruses), and the third of which are called lentiviruses and are non-cogenic which fuse into and kill their host cells, and this is what HIV is.

These lentivirus particles are spherical having a conical nucleoprotein covered by a bilayered phospholipid envelope with surface glycoprotein embedded. They are exogenously acquired viruses and are associated with slow, persistent and debilitating life long infections, inducing pathological changes in the immune system of the animals which result in severe immuno-deficiency syndromes.²

In the eighth part of his theory, Duesberg is saying that the contagious rate from HIV infection to AIDS depends greatly on the country and risk group membership, so HIV isn't sufficient to cause AIDS.¹ What we know is that HIV is directly correlated to the lifestyle risk factors such as homosexuality, drug use, and continued non-protective heterosexual activity. So in Africa, where condoms are not commonly used, there is an equal distribution of AIDS between the sexes. Whereas in the United States, AIDS began specifically among homosexuals because of the lack of condom use. Therefore, it is not country specific, but it is risk group specific. No matter what country you're in, if you engage in any one of the lifestyle risk group factors you have the chance of getting HIV. But it all comes down to HIV causing AIDS. For example, people who engage in homosexuality, drug use, etc., but aren't exposed to HIV don't get AIDS. On the other hand, people who aren't members of "risk groups" but are exposed to HIV get AIDS.³

Duesberg's ninth part to his theory claims that viruses are products of gradual evolution, therefore proposing that viruses HIV-1 and HIV-2 evolving within a few years is highly improbable.¹ What we know now is that HIV-1 is the more prevalent of the two kinds of viruses around the globe, but as Duesberg points out, there is another less virulent strain HIV-2, endemic to certain populations of West Africa. And this does represent a fascinating jigsaw puzzle that we don't know how to put together yet. So Duesberg's claim is the only one of the nine that could still be valid.

Now in 1996, since we know so much about HIV, Duesberg's theories no longer hold true with the exception of the ninth postulate. It is clear that the advent of HIV really puzzled Duesberg, and made him somewhat of an ancient retrovirologist. HIV does not fit Koch's postulates. It is a new type of virus for a new age in time, and it needs to be dealt with by virologists whom have an open mind, and are ready for any surprises that they may run into, leaving Mr. Duesberg "in the dust."

Footnotes

¹P. Duesberg, 1988. HIV is not the cause of AIDS. Science 241: 514-516; W. Blattner, R.C. Gallo, H.M. Temin, 1988. HIV Causes AIDS. Science 241: 514-516; P. Duesberg, 1991. AIDS epidemiology: Inconsistencies with human immunodeficiency virus and infectious disease. Proc. Natl. Acad. Sci. 88: 1575-1579.

²Welcome back to Vineet's WWW Hub for Chemistry at gupta@chem.Rochester.Edu.

³Duesberg Risk Group Theory: Califor@NetCom.ComSun (1995).

⁴Moore J., 1996. A Duesberg, Adieu!. Nature 380: 293-294.