My talk to the PhD students NRP at the Doctoral Training Programme Summer Conference 2015, The Assembly House, Norwich, Thursday 18th June. Notes and acknowledgments at http://kamounlab.tumblr.com/post/121748816600/what-are-world-class-science-outputs

1. What are world class scientific outputs?
Sophien Kamoun
http:KamounLab.net
@KamounLab

2. Why am I a scientist?

3. My inspiration…
“Je cherche à comprendre”
“I seek to understand”
Jacques Monod

4. I appreciate the power of science…
• There is a reality out there and
science can unravel it
• “We have a moral duty to
distinguish sense from nonsense”
– Massimo Pigliucci
• Science is predictive – key
difference between science and
pseudoscience

5. …and my motivation is curiosity
• As a scientist, I am in the business
of knowledge
• I have an addiction to knowledge. I
need to know: How do living
organisms work? How did they get
this way?
• My job is to generate knowledge to
advance science and influence
others to pursue new directions and
generate their own knowledge
• My job is also to communicate this
knowledge

6. Communication
We must communicate our discoveries to other
scientists, the government, the public etc.
!
Otherwise the impact will be quasi-nil

7. Publications!
• Main medium through which we
communicate our science
• Writing forces you to think
harder and precisely formulate
your work and contributions
• An archived document that
enables others to be inspired
and build on your research (or
dispute it)
• Publications come in many
forms these days
• Publish or perish!

8. How do we recognise world class publications?

9. confirmation
influence / impact

10. How to evaluate papers?
Judge publications on their own merit
Don’t use journals as proxy
Article-level metrics

11. The Leiden Manifesto
for research metrics
“Do not use journal-based metrics, such as Journal Impact
Factors, as a surrogate measure of the quality of individual
research articles, to assess an individual scientist’s contributions,
or in hiring, promotion, or funding decisions.”

12. Death to the impact factor
Misused and abused
Crude statistically flawed metric
Skewed by few highly cited papers

13. The weakening relationship between the Impact Factor
and papers’ citations in the digital age
George A. Lozano, Vincent Lariviere, Yves Gingras
y = 0.0011x - 1.9418
r2 = 0.4666
y = 0.003x - 5.7759
r2 = 0.579
y = -0.0049x + 9.9863
r2 = 0.4788
0,00
0,05
0,10
0,15
0,20
0,25
0,30
0,35
1900 1920 1940 1960 1980 2000 2020
Annualcoefficientofdetermination(r2)
Coefficient of determination (r2
) between the impact factor of journals and the two-year citation rate of their papers from 1902 to 2009, for al
and medical sciences journals.
0,25

14. Citations
• Most popular article-level metric
• Vary widely between fields of science
• Review articles get more cited
• Time dependent - take time to
accrue
• Retracted papers still get cited
(zombie papers)
• etc.
• But impact somewhat correlates
with citations - imagine a paper
that’s hardly cited

15. Highly Cited Papers
• Thomson Reuters Essential
Science Indicators℠ (ESI)
• Rank in top 1% by citations for
field and year indexed in the Web
of Science
• 21 broad fields defined by sets of
journals
• Papers are weighed against others
in the same cohort
• One example of article level
metrics

16. Where to publish?
• Aim as high as you reasonably can but don't become
obsessed with glamour magazines (glam-mags)
• Is your work relevant to a broad readership or is it more
appropriate to specialists?
• Consider “fit” not just journal prestige
• Do you like what you read in the journal?
• Open access papers get more widely read and cited

17. • Journals have declining influence in the digital age
• Open web: anybody can read your work if it’s open access
• Rise of the megajournals and preprint archives

18. You want impact!
• Impact is not just
about publishing in
glam-mags
• reach out to a wider
audience, media
exposure etc.
• Social media: twitter,
facebook etc.
• Alternative metrics

19. • Many bad papers get published in Nature, Science & Cell
• Don’t assume it’s flawless because it’s in a glam-mag
• Judge papers on their own merit
• Remember, time will tell!
A Bacterium That Can Grow by Using
Arsenic Instead of Phosphorus
Felisa Wolfe-Simon,1,2
* Jodi Switzer Blum,2
Thomas R. Kulp,2
Gwyneth W. Gordon,3
Shelley E. Hoeft,2
Jennifer Pett-Ridge,4
John F. Stolz,5
Samuel M. Webb,6
Peter K. Weber,4
Paul C. W. Davies,1,7
Ariel D. Anbar,1,3,8
Ronald S. Oremland2
Life is mostly composed of the elements carbon, hydrogen, nitrogen, oxygen, sulfur, and
phosphorus. Although these six elements make up nucleic acids, proteins, and lipids and thus
the bulk of living matter, it is theoretically possible that some other elements in the periodic
table could serve the same functions. Here, we describe a bacterium, strain GFAJ-1 of the
Halomonadaceae, isolated from Mono Lake, California, that is able to substitute arsenic for
phosphorus to sustain its growth. Our data show evidence for arsenate in macromolecules that
normally contain phosphate, most notably nucleic acids and proteins. Exchange of one of the
major bio-elements may have profound evolutionary and geochemical importance.
B
iological dependence on the six major
nutrient elements carbon, hydrogen, nitro-
gen, oxygen, sulfur, and phosphorus (P)
is complemented by a selected array of other ele-
ments, usually metals or metalloids present in
trace quantities that serve critical cellular func-
tions, such as enzyme co-factors (1). There are
many cases of these trace elements substituting
for one another. A few examples include the sub-
stitution of tungsten for molybdenum and cad-
mium for zinc in some enzyme families (2, 3) and
copper for iron as an oxygen-carrier in some ar-
thropods and mollusks (4). In these examples and
others, the trace elements that interchange share
chemical similarities that facilitate the swap. How-
ever, there are no prior reports of substitutions
for any of the six major elements essential for
life. Here, we present evidence that arsenic can
be incorporated into some early steps in the path-
ways [(6) and references therein]. However, it is
thought that downstream metabolic processes are
generally not compatible with As-incorporating
molecules because of differences in the reactiv-
ities of P and As compounds (8). These down-
stream biochemical pathways may require the
more chemically stable P-based metabolites; the
lifetimes of more easily hydrolyzed As-bearing
analogs are thought to be too short. However,
given the similarities of As and P—and by anal-
ogy with trace element substitutions—we hypoth-
esized that AsO4
3–
could specifically substitute
for PO4
3–
in an organism possessing mechanisms
to cope with the inherent instability of AsO4
3–
compounds (6). Here, we experimentally tested
this hypothesis by using AsO4
3–
, combined with
no added PO4
3–
, to select for and isolate a mi-
crobe capable of accomplishing this substitution.
Geomicrobiology of GFAJ-1. Mono Lake,
located in eastern California, is a hypersaline and
alkaline water body with high dissolved arsenic
concentrations [200 mM on average (9)]. We used
lake sediments as inocula into an aerobic defined
artificial medium at pH 9.8 (10, 11) containing
10 mM glucose, vitamins, and trace metals but no
added PO4
3–
or any additional complex organic
supplements (such as yeast extract or peptone),
with a regimen of increasing AsO4
3–
additions
initially spanning the range from 100 mM to 5 mM.
These enrichments were taken through many
decimal-dilution transfers, greatly reducing any
potential carryover of autochthonous phosphorus
5µm
CA
0.05
0.10
0.15
0.20
0.25
0.30
OD680
RESEARCH ARTICLE
onJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfromonJune16,2015www.sciencemag.orgadedfrom
ARTICLE doi:10.1038/nature12968
Stimulus-triggered fate conversion of
somatic cells into pluripotency
Haruko Obokata1,2,3
, Teruhiko Wakayama3
{, Yoshiki Sasai4
, Koji Kojima1
, Martin P. Vacanti1,5
, Hitoshi Niwa6
, Masayuki Yamato7
& Charles A. Vacanti1
Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency
(STAP), which requires neither nuclear transfer nor the introduction of transcription factors. In STAP, strong external
stimuli such as a transient low-pH stressor reprogrammed mammalian somatic cells, resulting in the generation of plu-
ripotent cells. Through real-time imaging of STAP cells derived from purified lymphocytes, as well as gene rearrange-
ment analysis, we found that committed somatic cells give rise to STAP cells by reprogramming rather than selection.
STAP cells showed a substantial decrease in DNA methylation in the regulatory regions of pluripotency marker genes.
Blastocyst injection showed that STAP cells efficiently contribute to chimaeric embryos and to offspring via germline
transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from STAP cells. Thus, our
findingsindicatethatepigeneticfatedeterminationofmammaliancellscanbemarkedlyconvertedinacontext-dependent
manner by strong environmental cues.
In the canalization view of Waddington’s epigenetic landscape, fates
of somatic cells are progressively determined as cellular differentiation
proceeds, like going downhill. It is generally believed that reversal of
differentiated statusrequires artificial physical or genetic manipulation
of nuclear function such as nuclear transfer1,2
or the introduction of
multiple transcription factors3
. Here we investigated the question of
whether somatic cells can undergo nuclear reprogramming simply in
response to external triggers without direct nuclear manipulation. This
type of situation is known to occur in plants—drastic environmental
changescanconvertmaturesomaticcells(forexample,dissociatedcarrot
cells) into immature blastema cells, from which a whole plant structure,
including stalks and roots, develops in the presence of auxins4
. A chal-
lengingquestioniswhetheranimalsomaticcellshaveasimilarpotential
that emerges under special conditions. Over the past decade, the pres-
ence of pluripotent cells (or closely relevant cell types) in adult tissues
has been a matter of debate, for which conflicting conclusions have
beenreportedbyvariousgroups5–11
.However,nostudysofarhasproven
that such pluripotent cells can arise from differentiated somatic cells.
HaematopoieticcellspositiveforCD45(leukocytecommonantigen)are
typicallineage-committedsomaticcellsthatneverexpresspluripotency-
related markers such as Oct4 unless they are reprogrammed12,13
. We
therefore addressed the questionof whether splenic CD451
cells could
acquire pluripotency by drastic changes in their external environment
such as those caused by simple chemical perturbations.
Low pH triggers fate conversion in somatic cells
CD451
cells were sorted by fluorescence-activated cell sorting (FACS)
from the lymphocyte fraction of postnatal spleens (1-week old) of
C57BL/6 mice carrying an Oct4-gfp transgene14
, and were exposed
to various types of strong, transient, physical and chemical stimuli
(described below). We examined these cells for activation of the Oct4
promoter after culture for several days in suspension using DMEM/F12
medium supplemented with leukaemia inhibitory factor (LIF) and B27
(hereafter called LIF1B27 medium). Among the various perturbations,
wewereparticularlyinterestedinlow-pHperturbationsfortworeasons.
First, as shown below, low-pH treatment turned out to be most effective
for the induction of Oct4. Second, classical experimental embryology
hasshownthatatransientlow-pHtreatmentunder‘sublethal’conditions
can alter the differentiation status of tissues. Spontaneous neural conver-
sion from salamander animal caps by soaking the tissues in citrate-based
acidic medium below pH 6.0 has been demonstrated previously15–17
.
Without exposure to the stimuli, none of the cells sorted with CD45
expressedOct4-GFPregardlessofthecultureperiodinLIF1B27medium.
In contrast, a 30-min treatment with low-pH medium (25-min incuba-
tion followed by 5-min centrifugation; Fig. 1a; the most effective range
was pH 5.4–5.8; Extended Data Fig. 1a) caused the emergence of sub-
stantialnumbersofsphericalclustersthatexpressedOct4-GFPinday-7
culture(Fig.1b).SubstantialnumbersofGFP1
cellsappearedinallcases
performed with neonatalsplenic cells (n 5 30 experiments). The emer-
genceofOct4-GFP1
cellsattheexpenseofCD451
cellswasalsoobserved
by flow cytometry (Fig. 1c, top, and Extended Data Fig. 1b, c). We next
fractionated CD451
cells into populations positive and negative for
CD90(Tcells),CD19(Bcells)andCD34(haematopoieticprogenitors18
),
and subjected them to low-pH treatment. Cells of these fractions,
including T and B cells, generated Oct4-GFP1
cells at an efficacy com-
parable to unfractionated CD451
cells (25–50% of surviving cells on
day 7), except for CD341
haematopoietic progenitors19
, which rarely
produced Oct4-GFP1
cells (,2%; Extended Data Fig. 1d).
Among maintenance media for pluripotent cells20
, the appearance
of Oct4-GFP1
cells was most efficient in LIF1B27 medium, and did
not occur in mouse epiblast-derived stem-cell (EpiSC) medium21,22
(Extended Data Fig. 1e). The presence or absence of LIF during days
0–2 did not substantially affect the frequency of Oct4-GFP1
cell gen-
eration on day 7 (Extended Data Fig. 1f), whereas the addition of LIF
during days 4–7 was not sufficient, indicating that LIF dependency
started during days 2–4.
1
Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 2
Laboratory for Cellular Reprogramming,
RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 3
Laboratory for Genomic Reprogramming, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 4
Laboratory for
Organogenesis and Neurogenesis, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 5
Department of Pathology, Irwin Army Community Hospital, Fort Riley, Kansas 66442, USA.
6
Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental biology, Kobe 650-0047, Japan. 7
Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical
University, Tokyo 162-8666, Japan. {Present address: Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
RETRACTED

20. #arseniclife - what happened?
!
• Postpublication peer review (PPPR)
• Addressed flaws of pre-pub peer review
• Social media and blogs

21. #arseniclife - what happened?
!
• Postpublication peer review (PPPR)
• Addressed flaws of pre-pub peer review
• Social media and blogs

22. M I C R O B I A L E C O L O G Y
The microbiome of uncontacted Amerindians
Jose C. Clemente,1,2
* Erica C. Pehrsson,3
* Martin J. Blaser,4,5
Kuldip Sandhu,5†
Zhan Gao,5
Bin Wang,3
Magda Magris,6
Glida Hidalgo,6
Monica Contreras,7
Óscar Noya-Alarcón,6
Orlana Lander,8
Jeremy McDonald,9
Mike Cox,9
Jens Walter,10‡
Phaik Lyn Oh,10
Jean F. Ruiz,11
Selena Rodriguez,11
Nan Shen,1
Se Jin Song,12
Jessica Metcalf,12
Rob Knight,12,13§
Gautam Dantas,3,14
M. Gloria Dominguez-Bello5,7,11¶
Most studies of the human microbiome have focused on westernized people with life-style practices that decrease
microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We
characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami
Amerindian village with no documented previous contact with Western people. These Yanomami harbor a micro-
biome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their
isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to
antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer
resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that western-
ization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the
human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mo-
bilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need
for extensive characterization of the function of the microbiome and resistome in remote nonwesternized popula-
tions before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.
INTRODUCTION
Host-microbial interactions are important determinants of host phys-
iology, including immune responses, metabolic homeostasis, and be-
havior (1–4). Microbiota transplantation can transfer phenotypes such
as nutritional status from donor to recipient (5, 6), indicating that al-
tered microbial communities can therefore cause, as well as result from,
altered physiological states. Despite increasing evidence that the micro-
biome has important roles in human health, we do not yet know the
extent to which the human microbiome has changed during the adop-
tion of life-styles associated with westernization. Here, we described the
microbiome from Yanomami subjects in the Amazon with no previous
report of contact with non-Yanomami. The Yanomami were originally
mountain people who were first contacted in the mid-1960s, and who
continue to live seminomadic hunter-gatherer life-styles in the Amazon
jungle. In Venezuela, they inhabit a region protected from development,
and many still inhabit uncharted villages in the vast mountainous
Yanomami territory (7). These remote populations of hunter-gatherers
have life-styles similar to those of our human ancestors, and are unex-
posed to modern practices known to exert antimicrobial effects.
For instance, pharmacologic-dose antibiotic exposure is nearly ubiq-
uitous worldwide, and all human microbiota studied to date, remote or
industrialized, harbor diverse antibiotic resistance (AR) genes (8, 9). Al-
though AR genes have been computationally predicted in ancient oral
microbiota (10), functional resistance from the preantibiotic era re-
mains largely uncharacterized. These subjects from an uncontacted
community therefore represent a unique proxy for the preantibiotic
era human resistome. Here, we characterized the microbiome and resis-
tome of these subjects, and compared them to those of othernon-isolated
populations. Samples of the oral cavity (n = 28), forearm skin (n = 28),
and feces (n = 12) were obtained from 34 of the 54 villagers (table S1) at
thetimeofthefirstmedicalexpeditiontoanisolated,previouslyuncharted
village in the High Orinoco state of Venezuela. The age of the subjects
was between 4 and 50 years, as estimated by Yanomami health workers.
1
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount
Sinai, New York, NY 10029, USA. 2
Immunology Institute, Icahn School of Medicine at
Mount Sinai, New York, NY 10029, USA. 3
Center for Genome Sciences & Systems Biology,
Washington University School of Medicine, St. Louis, MO 63108, USA. 4
Laboratory Service,
5
2015 © The Authors, some rights reserved;
exclusive licensee American Association for
the Advancement of Science. Distributed
under a Creative Commons Attribution
NonCommercial License 4.0 (CC BY-NC).
10.1126/sciadv.1500183
R E S E A R C H A R T I C L E

23. M I C R O B I A L E C O L O G Y
The microbiome of uncontacted Amerindians
Jose C. Clemente,1,2
* Erica C. Pehrsson,3
* Martin J. Blaser,4,5
Kuldip Sandhu,5†
Zhan Gao,5
Bin Wang,3
Magda Magris,6
Glida Hidalgo,6
Monica Contreras,7
Óscar Noya-Alarcón,6
Orlana Lander,8
Jeremy McDonald,9
Mike Cox,9
Jens Walter,10‡
Phaik Lyn Oh,10
Jean F. Ruiz,11
Selena Rodriguez,11
Nan Shen,1
Se Jin Song,12
Jessica Metcalf,12
Rob Knight,12,13§
Gautam Dantas,3,14
M. Gloria Dominguez-Bello5,7,11¶
Most studies of the human microbiome have focused on westernized people with life-style practices that decrease
microbial survival and transmission, or on traditional societies that are currently in transition to westernization. We
characterize the fecal, oral, and skin bacterial microbiome and resistome of members of an isolated Yanomami
Amerindian village with no documented previous contact with Western people. These Yanomami harbor a micro-
biome with the highest diversity of bacteria and genetic functions ever reported in a human group. Despite their
isolation, presumably for >11,000 years since their ancestors arrived in South America, and no known exposure to
antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer
resistance to synthetic antibiotics and are syntenic with mobilization elements. These results suggest that western-
ization significantly affects human microbiome diversity and that functional AR genes appear to be a feature of the
human microbiome even in the absence of exposure to commercial antibiotics. AR genes are likely poised for mo-
bilization and enrichment upon exposure to pharmacological levels of antibiotics. Our findings emphasize the need
for extensive characterization of the function of the microbiome and resistome in remote nonwesternized popula-
tions before globalization of modern practices affects potentially beneficial bacteria harbored in the human body.
INTRODUCTION
Host-microbial interactions are important determinants of host phys-
iology, including immune responses, metabolic homeostasis, and be-
havior (1–4). Microbiota transplantation can transfer phenotypes such
as nutritional status from donor to recipient (5, 6), indicating that al-
tered microbial communities can therefore cause, as well as result from,
altered physiological states. Despite increasing evidence that the micro-
biome has important roles in human health, we do not yet know the
extent to which the human microbiome has changed during the adop-
tion of life-styles associated with westernization. Here, we described the
microbiome from Yanomami subjects in the Amazon with no previous
report of contact with non-Yanomami. The Yanomami were originally
mountain people who were first contacted in the mid-1960s, and who
continue to live seminomadic hunter-gatherer life-styles in the Amazon
jungle. In Venezuela, they inhabit a region protected from development,
and many still inhabit uncharted villages in the vast mountainous
Yanomami territory (7). These remote populations of hunter-gatherers
have life-styles similar to those of our human ancestors, and are unex-
posed to modern practices known to exert antimicrobial effects.
For instance, pharmacologic-dose antibiotic exposure is nearly ubiq-
uitous worldwide, and all human microbiota studied to date, remote or
industrialized, harbor diverse antibiotic resistance (AR) genes (8, 9). Al-
though AR genes have been computationally predicted in ancient oral
microbiota (10), functional resistance from the preantibiotic era re-
mains largely uncharacterized. These subjects from an uncontacted
community therefore represent a unique proxy for the preantibiotic
era human resistome. Here, we characterized the microbiome and resis-
tome of these subjects, and compared them to those of othernon-isolated
populations. Samples of the oral cavity (n = 28), forearm skin (n = 28),
and feces (n = 12) were obtained from 34 of the 54 villagers (table S1) at
thetimeofthefirstmedicalexpeditiontoanisolated,previouslyuncharted
village in the High Orinoco state of Venezuela. The age of the subjects
was between 4 and 50 years, as estimated by Yanomami health workers.
1
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount
Sinai, New York, NY 10029, USA. 2
Immunology Institute, Icahn School of Medicine at
Mount Sinai, New York, NY 10029, USA. 3
Center for Genome Sciences & Systems Biology,
Washington University School of Medicine, St. Louis, MO 63108, USA. 4
Laboratory Service,
5
2015 © The Authors, some rights reserved;
exclusive licensee American Association for
the Advancement of Science. Distributed
under a Creative Commons Attribution
NonCommercial License 4.0 (CC BY-NC).
10.1126/sciadv.1500183
R E S E A R C H A R T I C L E

24. The importance
of wrong
• Our goal is to
generate robust
knowledge to
advance science
• “I was wrong” should
not be taboo
• Respond quickly,
admit error, make
correction

25. To sum up
• You’re in the business of
generating and
disseminating knowledge
• World class outputs
stand the test of time
and make a difference
• Focus on generating and
disseminating robust
knowledge
• You make it world class!

26. A new reward culture? YOU can make it happen!