READING THE DOLLY PAPER & PAPER
CRITIQUE GUIDELINES
I am
“Ewe”nique!!!
Giles & Knight. News. Nature 2003
Viable offspring derived from fetal &
adult mammalian cells. Wilmut et al.
1997. Nature.
TITLE & ABSTRACT
INTRODUCTION
INTRODUCTION
RESULTS
METHODS
RESULTS
DISCUSSION
REFERENCES
1. Reading the Title and Abstract
 What question are they asking?
 How did they ask it?
 Techniques used
Are the techniques the right ones?
 What were their results?
What would bolster these results?
 What were their conclusions?
Are they the right conclusions? Why or why not?
What else do they need? What would you do?
2. Reading the Introduction
• Important background for people not in the
same field
• How the authors think their work fits into their
field
– The Big Picture
– Why the question is being asked
– Why certain techniques were chosen
3. Reading the Results
 One figure at a time: What is the smaller question
being asked?
 A. What technique was used
 B. What results were obtained - what does the figure
show?
 C. What conclusions were drawn from the results
 D. Are the conclusions appropriate? How does the
result help to answer the question?
 Think: What else would I do? How?
4. Reading the Discussion
 Often a brief summary of the findings in the paper
 The experimenters’ conclusions about their
material
 Are they right? Are they reaching?
 Think about the real conclusions of the data given
 What could convince you - think of “Future
experiments” that need to be done
 and write them down!
5. Reading The Methods Section
 Extra details about experiments
 Provides other researchers with enough information
to replicate experiments
 Often full of jargon and abbreviations, and targeted to
other scientists in the same field
 Usually reference previous work - more trips to the
library
 Why you should come to section!!
 Questions: ask your TAs!
Review Guidelines - Format
• 12 point font
• Standard (0.5 in) margins
• Single spaced
• ONE PAGE ONLY
- Anything on a second page will not be graded.
- Brevity is key!
•10 Points Total
Scoring - The Quick Stuff
 Background: 1 point
 Stick to info given in paper - no extra research
 Goal of Experiment: 1 point
 What were they trying to do? Why - Hypothesis?
 Explanation of experiment: 1 point
 What did they involve (broad methods) and what techniques were
employed?
 Interpretation of results: 1 point
 What do they mean? Do they support/argue against hypothesis?
 Correctness: 1 point
 Subjective point: 1 (grammar, spelling etc)
 Keep this section of your review brief (avoid wordiness!) and
in your own words
Scoring - The IMPORTANT Bit
 CRITIQUE: 2 points
 GOOD: What did the researchers do right or wrong? What
could they have done better? Be specific!
 BAD (0 points):
 “The researchers present evidence both for and against their
hypothesis. They accept the hypothesis, but do not explain (not
very clearly at least) why the “for” evidence is more significant
than the “against” evidence.”
 FUTURE EXPERIMENTS: 2 points
 GOOD: Design an additional experiment that addresses
the deficiencies in the paper or provides corroborative
evidence for the conclusions it draws. Be specific and
creative!
 BAD (0 points):
 “Further work must be done to determine which of these models,
if any, is the correct one.”
Dolly Paper Example Critique
Part D”ewe”
Giles & Knight. News. Nature 2003
1. Background - 1PT
 Embryonic nuclei rapidly lose ability to generate a tadpole
as they age (Briggs & King, 1965)
 See Gilbert, chapter 4
 Nuclei from adult keratinocytes can give rise to tadpoles,
but not to adults. (Gurdon et al., 1975)
 Nuclei from cultured embryonic cells induced into
quiescence can give rise to lambs. (Wilmut 1996, 1997)
 Quiescence = cell inactivity (G0)
In your OWN words! Condense!!! *Only a few sentences*
2. Goal of experiment - 1PT
Hypothesis:
“We suggested that inducing the donor cell to exit the growth phase
causes changes in chromatin structure that facilitate
reprogramming of gene expression and that development would be
normal if nuclei are used from a variety of differentiated donor cells
in similar regimes.”
• Wilmut et al. hypothesize mammalian nuclei can generate viable
offspring if they are properly reprogrammed by being forced to exit
from the cell cycle into G0.
Goal:
“Here we investigate whether normal development to term is
possible when donor cells derived from fetal or adult tissue are
induced to exit the growth cycle and enter the G0 phase of the cell
cycle before nuclear transfer.”
• In this study, Wilmut et al. test the ability of nuclei from cells at
different stages of development to generate a complete lamb.
3. Explanation of Experiments - 1PT
 Three different cell types were used as nuclear donors:
 Embryonic cells were cultured from a 9 day old Poll Dorset
embryo
 Fetal cells were derived from a 26 day old Black welsh Mountain
fetus.
 Mammary gland cells were obtained from a 6 yr old Finn Dorset
ewe.
 Donor cells were checked for the correct number of
chromosomes (54) and forced to exit the cell cycle through
serum starvation.
 In the presence of serum (growth factors), cells progress through
the cell cycle and divide rapidly
 In the absence of serum (starvation), cells can survive by entering
the G0 phase and remaining quiescent
 Nuclear Transfer
 The cloning technique.
4. Interpretation of Results - 1PT
•
Wilmut et al. examined the cultures of
nuclear donor cells with phase
contrast microscopy and based on
morphology, determined that they
were not embryonic stem cells.
•
Microsatellite analysis showed that
the resulting lambs were indeed
clones since their polymorphisms
were identical to the nuclear donor
cells and not to the surrogate ewes.
5. Critique - 2PTS
Have they supported their hypothesis? (Read it carefully)
“We suggested that inducing the donor cell to exit the growth phase
causes changes in chromatin structure that facilitate reprogramming
of gene expression & that development would be normal if nuclei are
used from a variety of differentiated donor cells in similar regimes.”
Critique, cont’d:
Look at figures closely!
Critique, cont’d:
6.

Future Experiments - 2PTS
Mammary epithelium cells can divide quickly and the source they used was a
mixed population from a pregnant ewe. Test the ability of a differentiated cell
that is unlikely to divide quickly such as nuclei from neurons. If cell cycle is the
only thing that really matters you should be able to get embryos.
These are not the result of nuclear transfer!
http://www.nerdie.com/animalcloning.html
Office Hour Information
 Jon Valencia
 jev@caltech.edu
 Monday 5-6PM (the following week)
 Thursday 5-6PM (the current week)
 Building & Room: Kerckhoff 017