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PII: s0307-4412 (96)00022-2 biochemistry, some will become research scientists.


Therefore the curriculum covers a wide range of subjects
Students' Bibliographic Research: Competition
during the first years and clinical or research-oriented
Enhances Results
subjects are taken towards the end of the program.
NORA ENGEL,* GABRIEL STEKOLSCHIK, Table 1 provides an overview of the structure of the
FERNANDO MENDIVE and SERGIO BARANZINI degree course. Some of the subjects the students have
taken by the time they reach the fourth year are:
Cdtedra de Gen~tica y Biologla Molecular,
Chemistry (general, inorganic, organic, analytical, bio-
Facultad de Farmacia y Bioquimica, logical), Mathematics and Statistics, Biology, Anatomy,
Universidad de Buenos Aires, Physiology, Physics, Physico-chemistry and
Buenos Aires, Argentina Microbiology.
Because of the fact that the students have no molecular
Introduction biology background at this level, and have never come into
A bibliographic search on an area of interest and applica- contact with the scientific literature, remembering that
tion in molecular biology was proposed as part of a course the latter is mostly in English not Spanish, their native
called Basics of Genetics and Molecular Biology, which is tongue, we decided to elaborate a non-conventional
an obligatory four-month course for fourth year bio- teaching methodology in order to motivate them for this
chemistry students. The general objectives were to induce activity. We feel that any methodology that arouses the
the students to learn to come into contact with the scien- students to participate actively is positive for their scien-
tific literature and to conduct a bibliographic search on a tific training. We also believe that the capacity to interpret
specified subject. scientific papers involves skills which should be practiced.
Specific objectives, subjects and teaching methodolo- Therefore, we chose to propose a questions and answers
gies were left up to the teachers. We elaborated following contest based on a certain topic to be researched over the
specific objectives: duration of the course. The students are divided into
- - t h a t students learn to handle the different formats in working groups and in the contest, which is the final
which scientific information is available. activity, each of the student working groups asks and
- - that students come into contact with a research subject answers question in turn. According to the number of
beginning with the biological problem to be solved, the correctly answered questions, each group accumulates
different hypotheses offered, the experimental design and points, and the one which wins the contest gets a prize
the actual results arrived at so far, so as to transmit a from the other groups and automatically passes the
dynamic view of Molecular Biology, and Science in second of the two partial exams.
general.
- - that the students learn to analyze results, propose new
hypotheses and above all, new experimental approaches; Methodology
in other words, to stimulate their creativity. The teachers involved in the project carry out a biblio-
- - that students learn to select and organize the informa- graphic search previously in order to select an appropriate
tion obtained. subject. We choose topics that address general biological
Students that take our course are studying Bio- problems, especially those that have generated contro-
chemistry, which in the University of Buenos Aires is a versy and contrasting theories, especially if they have not
graduate program lasting an average of 6 years. Although yet been fully solved.
a large percentage of the graduates will work in clinical There are 3 four-hour classes devoted to the biblio-
graphic research during the four-month period of the
*Corresponding author. course, interspersed with the regular weekly lectures.

Table 1. Structure of the graduate studies in Biochemistry in the University of Buenos Aires
Year Subjects
First History and Philosophyof Science Mathematics I General ChemistryI
Introductionto Social Sciences Physics General ChemistryII
Second MathematicsII Anatomy Inorganic Chemistry
PhysicsII Histology Organic ChemistryI
Third Biostatistics Physiology Organic ChemistryII
Physics Chemistry Physiopathology Organic ChemistryIII
Fourth Radiochemistry Microbiology BiochemistryI
Genetics and MolecularBiology Immunology BiochemistryII
Fifth Pharmacology Clinical ChemistryI Bromatology
Toxicology Clinical ChemistryII Physiopathology
Sixth Students take 5 subjectsaccordingto the specializationchosen.They are: ClinicalBiochemistry,Basic Biochemistry,
Biotechnology,Bromatologyand Nutrition Immunologyand AgriculturalBiochemistry

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The first class consists of a presentation of the object- which has always been highly motivating for the students.
ives, methodology and type of evaluation. We give It addresses a problem everyone is interested in, since the
detailed information on how to gain access to the required origin and exact nature of the differencies between the
information: databases, libraries, Internet. The subject to sexes has probably been debated since prehistorical times.
be investigated is presented with a series of guiding ques- There is a rich history of contrasting theories on the basis
tions aimed at eliciting the students' prior knowledge on of sex determination. A scientific basis for sex determina-
the theme and at pointing out the need to apply Molecular tion was found with the appearance of the chromosome
Biology approaches to the research. Guidelines are given theory, and the advent of modern genetics and molecular
with regard to the limits for the retrieval, for example, if biology produced an important source of information.
the search should be carried out from a certain year Sex determination is part of the wider theme of mor-
onwards, or for experimentation on certain species. phogenesis and cellular differentiation as pathways
We then propose the contest, and ask the students to depending on the activity of sets of genes working within
divide into groups of 5 - 7 individuals (in our case, we interacting networks. Master regulatory genes generally
generally have four groups). The groups have the whole initiate cascades of gene activation, ultimately producing
period of the course (four months) to carry out the litera- structural patterns which lead to differentiation. These
ture search, select appropriate papers, extract the infor- genes are activated in response to different signals and act
mation and elaborate the questions to be asked to the as switches between programs of cellular development, or
other groups. between proliferation and differentiation. In mammals,
The second class is at half-term, for the purpose of whether the embryo will follow the male or female
guiding the different student groups, and answering any pathway is determined by the presence of the Y chromo-
technical questions they may have on the papers they have some, t which is the signal for the differentiation of testes
compiled. instead of ovaries. 2 Sex determination is amenable to
The last class is at the end of the term and consists of study because sex mutations are generally not lethal, ahd
the contest itself. During the actual contest, each group therefore detailed maps of the Y chromosome have been
must ask and answer a predetermined number of ques- constructed from the analysis of the genomes of sex-
tions (ie two rounds of questions for all the groups) on the reversed XX males and XY females. From these maps,
subject. Answers are assigned points according to their information was obtained leading to the cloning of several
accuracy and are evaluated by the asking group. The genes claimed to be the sex-determining region of the Y
teacher participates only in the case of disagreement chromosome. 3'4 Studies of evolutionary conservation of
between the asking and answering groups. the candidate genes and elucidation of their patterns of
Scores are assigned according to the following criteria: expression were carried out. Finally, the generation of XX
Correct answer: 2 points; incomplete answer: 1 point; mice transgenic for Sry, one of the candidate genes, which
wrong answer: 0 points; no answer: - 1 point. induced sex reversion and the appearance of testes, led to
The group which accumulates the highest score wins what seemed to be the conclusion of the long search?
the contest and automatically passes the second partial However, many new questions were raised as to what the
exam. signal for Sty induction was, and which were its function
and its downstream target genes, all subjects of current
research. For example, studies are underway on genes
Results which determine female specific functions and which are
Examples of subjects that have been used successfully for postulated to be negatively regulated by Sry. 6'7
this activity so far are: In the specific case of sex determination, in the intro-
ductory class at the beginning of the course, a diagram
• Sexual differentiation: original theories, discovery of representing the basis of the problem and a list of ques-
the ZFY and SRY genes, applications; tions is handed out to the students and they are asked to
• Production of mature immunoglobulins: genomic reor- study the diagram, identify the problem and answer the
ganization, regulation of expressed genes; questions intuitively, regardless of their actual knowledge
• Genetic bases of the variability of the AIDS virus. on the subject. The diagram consists of a drawing of two
There is a wide range of areas in which biological prob- sperm cells, one with an X chromosome and another with
lems are being solved through molecular biology tech- a Y chromosome, fertilizing an oocyte. The egg cell is
niques. Some of our projected subjects are: represented, and the two possible pathways are illustrated
• Regulation of cell proliferation, apoptosis and malig- with photographs on one hand, of a boy and further, a
nant transformation man, and on the other hand, of a girl and a woman.
• Gene therapy The questions are: (a) What is the initial determinant
• Pattern formation and morphogenesis of whether an embryo will develop into a male or a
• Neural development female? (b) If a chromosome is the determinant, what
region of the chromosome is involved? (c) How could you
In order to illustrate the activity, we would like to expand isolate the important region of the chromosome? (d)
on the example of sex determination. This is a subject What molecular mechanisms could be involved? (e) How

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could you demonstrate experimentally that a certain the research line and the questions that remain open are
region of a chromosome is in fact the sex determining elicited and written out on the blackboard.
region? The evaluation of the activity is carried out by two
When the group have had some time to think the ques- approaches. On the one hand, students are asked to fill
tionnaire over, a discussion is held among all the groups. out an anonymous opinion form grading the educational
At this point, they are encouraged to formulate their objectives of the bibliographic search: whether it aroused
hypotheses, even if their wording is inaccurate. The their participation, whether they felt they were more able
teacher takes note of the general ideas that have been to analyze scientific literature, whether they had gained
produced. the capacity to identify scientific problems, design experi-
After this discussion of the problem, a brief history of ments and interpret results, and whether the methodology
some of the theories regarding sex determination is given employed had been important in reaching the objectives
by the teacher. For example, some ancient philosophers stated on the first day of class. The majority of the
had theories that sex was determined according to students assigned the highest grade to each of these
whether the left or right testicle had produced the fertil- points. Table 2 gives the results of the opinion poll for the
izing sperm, environmental factors (temperature, direc- August-November 1995 students who partook in this
tion of the wind at the time of fertilization), etc. Although activity.
not true for mammals, temperature of embryonic On the other hand, the test taken by all the students
development is important for some species. excepting those who had won the contest was designed to
The path of development of this subject takes the evaluate the same points. It consists of a problem in the
students through the themes of the course syllabus. The format of a paper, with Introduction, Materials and
chromosome theory, chromosome mapping, the existence Methods and Results. It is elaborated by one of the
of genes, gene cloning, the study of their tissue-specific teachers on the basis of a research paper on a different
expression, and the targets for their function, are the con- topic, which is modified appropriately. The Discussion is
cepts that appear chronologically as the students follow left to the students, who are asked precisely to interpret
the research line. We circumscribe the bibliographic the results, discuss them in the light of the initial hypo-
search to work in humans and mice, since these two sys- thesis, and to propose future experiments to resolve
tems have generated mutually valuable information, and unanswered questions. This exam is handed in to be
in order to narrow the range of the search, which would graded by previously established criteria by the teacher.
otherwise be unmanageable. The students' performance in this test is generally very
By the time of the second class, the students have good. However we have no way to compare the grades
carried out the initial bibliographic search and have with those attained in former years, because the exams
obtained the most important papers. At that point, the were qualitatively different.
techniques used in the papers are becoming accessible to The first year that we used this methodology, we com-
them through the rest of the classes, but some doubts arise pared the number of papers obtained, the quality of the
and here the teacher's help is required. In addition, they questions and the level of attainment in the topic
are probably needing the references within the papers researched between two groups: one in which the contest
they have read and must in turn obtain this material. was used and one in which there was no competition and
During the third class, the contest takes place. The the final activity was simply to lecture on the subject. We
atmosphere is generally very competitive, but enjoyable. found that the number of papers read, the depth of the
The fact that it is the students that ask the questions questions and the level attained by the group of students
automatically adjusts the difficulty level to their who prepared for the contest was higher than in the
capacity. course in which the methodology did not include the
After the contest, and as a closure for the activity, the contest.
teacher produces the notes taken on the discussion of the
first day, and establishes a comparison between the infor- Discussion
mation retrieved through the search and the intuitive The retrieval of scientific literature requires learning
hypothesizing on the topic at the beginning. A summary of effective search procedures, evaluating the relative

Table 2. Results of the evaluation form responded to by students of 1995 course*


Item evaluated Distribution of opinions(%)
Excellent Good Regular Bad
Arousal of student participation 89.9 7.4 2.7 - -

Increase in the comprehension of scientific literature 92.6 2.8 3.7 0.9


Development of the capacity to identify a scientific problem, design an appropriate 87.1 3.7 5.5 3.7
experiment and interpret results
Importance of the methodology applied for the fulfillment of the objectives 95.4 3.7 0.9

*Three classes, totalling 109 students.

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importance of different articles published on a certain students' interest. We have found that the most appro-
subject and understanding of what is reported in the priate subjects are the ones with conflicting theories and
articles. These skills are essential for biochemistry multiple experimental approaches. These characteristics
students, and for graduates in any field. Although the allow the students to receive an impression of science, in
students taking our course are already in fourth year, they general, and molecular biology, in particular, as a
have not been in contact with scientific literature. As an dynamic, contemporary discipline.
integral part of our course, we include an initiation into The students are highly motivated by this methodology,
bibliographic research, which not only serves as a vehicle in spite of the difficulties emerging from the novelty of
for the consolidation of concepts in Genetics and Molec- interpreting scientific literature, added to the fact that
ular Biology, but also as an acquisition of skills which are there is a natural language barrier. The competitive
important for the students' scientific formation in general. nature of the contest seems to stimulate them very
In order to stimulate our students in this task, we use a much.
questions and answers contest between groups of students The first year we proposed this methodology, one of
investigating the bibliography on a certain topic. Games the classes rejected the proposal. Another class was
provide more than motivation: they build a closer divided into three groups of three people each, but one of
empathy between teachers and students. In this case, the them did not work enough to take part in the contest.
division into work groups also stimulates communication Therefore it was reduced to a competition between two
and cooperative learning. groups. However, this situation was commented on exten-
On the basis of our experience, there are several points sively in class and the groups who had fulfilled the goals
to be emphasized. We believe that the introductory class is clearly identified the problem and held the third group
essential in eliciting the cooperation of the students. The responsible. Further experiences demonstrated that if the
fact that we make it a point to explain the objectives in number of groups were larger, with at least five people
detail, to underline the philosophy of our choice and to each, these problems were less likely to affect the final
make the success of the contest clearly dependent on their outcome.
collaboration is decisive. We have been carrying out this activity for four years
At the point at which we introduce the biological and we are satisfied on the basis of the opinion polls and
problem with the question guide, and although the the results of the tests that the level of comprehension
students still have little background, the hypotheses they acquired by the students and the engagement in an active
propose and the methodology they envisage almost always form of research is very formative. We therefore conclude
anticipate what actually occurred in the research line. This that this activity is important in introducing students who
is highlighted in the last class by the teacher, who reminds will eventually be scientists to scientific literature, and to
the students of the discussion carried out in the first class the pathways of access to bibliography. The methodology
and induces them to compare their hypotheses with what employed is highly motivating and elicits the students'
they have discovered in the bibliography. It is useful and interest and participation successfully.
exciting for the students to realize that they have the
capacity to hypothesize and imagine ways in which to References
study the subject, and this somehow generates an identi- 1 Jacobs, PA and Strong, J A (1959) Nature 183,302-303
fication with the researchers. We also find that this activity 2 Jost, Jet al (1973) Recent Prog Horm Res 29, 1-41
during the first class anchors the subject onto their pre- 3 Sinclair, A Het al (1990) Nature 346, 240-244
4 Page, D C et al (1987) Cell 49, 595-602
vious concepts of biology, biological chemistry, and other 5 Koopman, P et al (1991) Nature 351, 117-121
subjects. 6 Wagner, T et al (1994) Cell 79, 1111-1120
The selection of the topics is crucial in arousing the 7 Luo, X et al (1994) Cell 77, 481-490

BIOCHEMICAL EDUCATION 24(3) 1996

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