Collaboration and Team Science
William G. Nelson, M.D., Ph.D.
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
• Research Mission at Johns
Hopkins
• High Performance Teams
• Metrics of Team Science Output
• Barriers Confronted by Research
Teams at Johns Hopkins
William G. Nelson, M.D., Ph.D.
Disclosures
Member
Cancer Scientific Advisory Council, AbbVie Inc.
Scientific Advisory Board, ProQuest Investments, Inc.
Ad Hoc Consultant
GlaxoSmithKline Inc., Merck and Co.
Licensed Intellectual Property
(with Johns Hopkins)
MDxHealth, Veridex, Inc., BioSante,
Inc.
The mission of Johns Hopkins
Medicine is to improve the health of
the community and the world by
setting the standard of excellence in
medical education, research and
clinical care.
Diverse and inclusive, Johns
Hopkins Medicine educates medical
students, scientists, health care
professionals and the public;
conducts biomedical research; and
provides patient-centered medicine
to prevent, diagnose and treat
human illness.
Vision: Johns Hopkins Medicine
provides a diverse and inclusive
environment that fosters intellectual
discovery, creates and transmits
innovative knowledge, improves
human health, and provides
medical leadership to the world.
Glossary
You, sir, are crap.
Science:
systematic knowledge of the physical world
gained through observation and experimentation
Research:
investigation or experimentation aimed at the
discovery and interpretation of facts, revision of
accepted theories or laws in the light of new
facts, or practical application of such new or
revised theories or laws
Health:
the condition of being sound in body, mind, or
spirit; freedom from physical disease or pain
“…Philosophy of science is
about as useful to
scientists as ornithology is
to birds…”
Richard P. Feynman
1918-1988
Pointed out that it is likely that
ornithological knowledge would be
of great benefit to birds, were it
possible for them to possess it.
Jonathan Schaffer
Australian National
University
Mission of the National Science Foundation
National Science Foundation Act of 1950 (Public Law 81-507)
set forth NSF's mission and purpose:
To promote the progress of science; to advance the national
health, prosperity, and welfare; to secure the national
defense....
The Act itself authorized and directed NSF:
• to support basic scientific research and research
fundamental to the engineering process
• to augment scientific and engineering research potential
• to strengthen science and engineering education programs
at all levels and in all the various fields of science and
engineering
Mission of the National Institutes of Health
To seek fundamental knowledge about the
nature and behavior of living systems and the
application of that knowledge to enhance health,
lengthen life, and reduce the burdens of illness
and disability
Impact of Cancer in the U.S.*
• About 44% of men and 38% of women will develop
cancer in their lifetimes
• 1,529,560 new cancer cases and
569,490 deaths new cancer cases
in 2010
St. George and the Dragon
• 569,490 cancer deaths in 2010
• 84% of all cases are diagnosed
after age 60
• 31% of all cases are diagnosed
after age 80
*American Cancer Society, Cancer Facts & Figures
2004 and 1997; Jemal A et al. CA Cancer J Clin 60:
277-300 Cancer
(2010)Society, Cancer Facts & Figures 2004 and 1997, citing NIH data
American
Raffaello Santi
c. 1506
Collaborative Research Achieved First Cancer Cures
• Lucy Wills discovered folic acid in
1937
• folic acid seemed to worsen acute
lymphoblastic leukemia (ALL) in
children
• in collaboration with Harriett Kilte
and Yellapragada Subbarao of
Lederle Laboratories, Sidney Farber
induced remissions in children with
ALL upon administration of antifolates aminopterin and amethopterin
(methotrexate) in 1948
Sidney Farber, MD
1903-1973
Lessons Learned About High Performance Teams
• a significant performance challenge energizes
teams
• leaders foster team performance best by building
performance ethic
• real teams always find ways for individuals to
contribute and gain distinction
• discipline within teams and across organizations
creates the conditions for team performance
The Performance Output/Impact of Teams
Common Approaches to Building Team Performance
• establish urgency and direction
• select members based on skill and skill potentialnot based on personality
• pay attention to initial interactions
• set clear rules of behavior
• identify a few immediate performance-oriented
tasks/goals
• challenge the group regularly with fresh facts/data
• spend lots of time together
• exploit positive feedback, recognition, and reward
SKCCC Vision
To accelerate the transformation of cancer care by
promoting the discovery of knowledge leading to
the prevention and cure of human cancers.
-Mission Captured in a Strategic Plan
Completed in 2010 and Accepted
by Johns Hopkins Medicine Leadership
Brief History
• 1968 - First formal cancer research program; Albert H. Owens,
M.D., Director
• 1973 - authorized by the Trustees of the University and Hospital
as academic Department and Hospital Functional Unit
• 1976 - Designated as NCI Comprehensive Cancer Center
• 1992 - Martin D. Abeloff, M.D. named Director
• 2001 - $153.9M naming gift from Sidney Kimmel
• 2008 - William G. Nelson, M.D., Ph.D. named Director
• 2011 - 50th year of NCI support for cancer research
SKCCC Membership
(building scientific teams to combat cancer)
•
254 SKCCC members from 28
Johns Hopkins Departments
– 95 additions/36 departures over
6 years
•
Membership requires Program
nomination and Executive
Committee approval
Basic Sciences
6%
Sch Engineering
2%
Sch Public Health
9%
Oncology
33%
Surgical Depts
17%
•
Increasing diversity: 39% of new
SKCCC members now non-white or
female
•
Membership Criteria:
̶
Principal Investigator (PI)/Project Leader of a peer-reviewed,
cancer-relevant grant
̶
Co-PI of a peer-reviewed, cancer-relevant grant
̶
Contributor to cancer clinical protocol development
̶
New faculty investigator with promise of meeting criteria for full
membership within 3 years
Other Med Depts
33%
SKCCC Programs
ACCRUALS/
NEW PTS
(2011)
# MEMBERS
FUNDING
PEER-REVIEWED (TOTAL)
Cancer Biology
29
$10.0M ($15.5M)
Hematologic Malignancies/BMT
29
$10.1M ($14.9M)
Cancer Immunology
29
$11.2M ($12.3M)
Viral Oncology
17
$6.0M ($6.4M)
Cancer Prevention & Control
31
$8.6M ($9.9M)
Chemical Therapeutics
26
$13.4M ($17.0M)
Prostate Cancer
32
$10.2M ($14.6M)
17.6%
Breast Cancer
28
$6.6M ($10.5M)
16.1%
Gastrointestinal Cancer
29
$9.0M ($14.8M)
33.8%
Upper Aerodigestive Cancer
26
$5.2M ($11.0M)
22.1%
Brain Cancer
17
$7.5M ($10.6M)
17.1%
Cancer Molecular & Functional
Imaging
25
$13.3M ($14.0M)
PROGRAM
53.3%
Use of SKCCC Facilities to Promote Team Science
Current Space: 621,160 ft2
• Clinical: 323,300 ft2
• Research: 222,000 ft 2
• Other: 75,860 ft2
Research Program
members are
co-located
to maximize
collaborative
interactions
Cancer Research at SKCCC
Metrics of Impact for Discipline-Based Programs
Metric
NCI Target
SKCCC Target
Inter-/intra-programmatic
publications
10%
15%
Program Project Grants
1-2
H-index/Node Factor/Other
To be determined
Program members with peerreviewed funding
80-85%
Original ideas translated to clinical
trials
Enumerate
Value added by Program over the
sum of individual investigators
Describe
Program Interactions Promote Team Science
Hematological Malignancies
Cancer Immunology
Cancer Biology
Viral Oncology
Non-Programmatically
Aligned
Cancer Prevention
and Control
Cancer Molecular and
Functional Imaging
Chemical
Therapeutics
Brain Cancer
Prostate Cancer
Upper Aerodigestive
Cancer
2006-2011
263 researchers
2032 collaborations
643 intra-Programmatic
1389 inter-Programmatic
Breast Cancer
GI Cancer
Program Interactions Promote Team Science
Hematological Malignancies
Cancer Immunology
Cancer Biology
Viral Oncology
Non-Programmatically
Aligned
Cancer Prevention
and Control
Cancer Molecular and
Functional Imaging
Chemical
Therapeutics
Brain Cancer
Prostate Cancer
Upper Aerodigestive
Cancer
2006-2011
263 researchers
2032 collborations
643 intra-Programmatic
1389 inter-Programmatic
Breast Cancer
GI Cancer
Cancer Research by High Performance Teams
at the SKCCC
• Cancer Center supports multiple collaborative transdisciplinary Research Programs
• Collaborative grants rose from 18 to 30 since 2005;
including 6 SPOREs, 7 P01s, 8 U01s, 5 U54s,1 U24,
1 P30, 2 P50s
• Meetings, seminars, retreats
• Many points of interactions between Research
Programs
Team Science Pays Off: Increases in NCI
Funding Despite Declining NCI Budget
NCI Funding Base
• $93.8M in NCI grants
• $59.8M in other NIH
grants
Million
• $203.6M in cancerrelevant grants
$100
$90
$80
$70
$60
$50
$40
$30
$20
$10
$0
$93.8
$75.6
$41.4
2000
2005
2010
Whole Exome Sequences
of 100 Human Cancers*
11 colorectal cancers
11 breast cancers
24 pancreas cancers
22 gliomas
22 meduloblastomas
SKCCC
2 leukemias
1 breast cancer
Washington
University
British Columbia
Cancer Research
Centre
1 breast cancer
4 granulosa cell tumors
3142 mutated genes
286 tumor suppressors
33 oncogenes
1 lung cancer Sanger
1 melanoma
Sanger Institute
Science, Feb 16, 2001
*Vogelstein B AACR Annual Meeting (2010)
High Dimensional Sequencing of Cancer Genomes
Reveals Both Common and Rare Gene Defects in
Human Cancers*
PI3KCA
PI3KCA
TP53
*Wood LD et al. Science 318: 1108-13 (2007)
TP53
Genome-Wide Epigenetic Alterations in
Metastases from Men Dying of Prostate Cancer*
Hypermethylation
(versus normal
tissues)
Hypomethylation
(versus normal
tissues)
*Aryee MJ et al. Sci.
Transl. Med. In press
(2013)
Biomarker Discoveries
germline DNA variants
somatic DNA mutations, translocations, etc.
somatic DNA somatic methylation changes
RNA expression changes, splice variants
protein expression changes
Translational Development
of Molecular Biomarkers
at SKCCC:
What are the Challenges?
Regulatory/Systems Considerations
CLIA, biospecimen collection/
archiving, HIPAA, health record
information technology
Biomarker Assay Platforms
DNA Beaming, PARE,
MSP, nanoMSP, MOB,
COMPARE, GEMINI
Integration into Clinical Practice
Test
Marker
Specimen
Company
Disease
Indication
PCA3
RNA
urine
Dianon
prostate
cancer
predicts prostate
biopsy outcome
MGMT
methylation
DNA
tissue
MDxHealth
glioblastoma
predicts response
to temozolomide
GSTP1
methylation
DNA
urine
tissue
LabCorp
MDxHealth
prostate
cancer
predicts prostate
biopsy outcome
AMACR
protein
tissue
many
prostate
cancer
diagnosis aid
Improving Cancer Health at a Population Scale:
New Types of Teams are Needed
Organization
(Characteristics)
Population Size
Johns Hopkins Community Physicians
(Primary Care Provider Network)
>260,000
Johns Hopkins Priority Partners
>185,000
(Medicaid Health Maintenance Organization)
Johns Hopkins Employee Health Program
>50,000
(Health Insurance Plan)
Johns Hopkins US Family Health Plan
Enrolling
(Provider to US Government and Military
Employees and Families)
Cancer Prevention and Control Program members already working
to establish cancer screening guidelines and improve screening
performance- first project focuses on reducing over-screening for
prostate cancer among elderly men
Prostate Cancer Program
High Performance Team
Team Science Pays Off
Discoveries that would be
Unthinkable Without the
Diverse Expertise Captured in
High Performance Teams
Digoxin and Prostate
Cancer*
-log(EC50)
-log(IC
>20 uM
*Platz EA et al. Cancer Discov. 1 :68-77 (2011)
<5 nM
Evolution to Fully-Integrated Team Science
De Marzo – Nelson – Yegnasubramanian
Laboratory for the Molecular Pathogenesis and
Molecular Pharmacology of Prostate Cancer
Angelo M. De Marzo,
M.D., Ph.D.
William G. Nelson,
M.D., Ph.D.
Srinivasan Yegnasubramanian,
M.D., Ph.D.
Individual Performance is Rewarded by Promotion
and Resource Allocation in an Academic Setting
Use of Publication Metrics by Academic Promotions Committees*
Total number of publications; number first/last author
Average citations for publications; citations for first/last
author papers
H-index
• Hirsch index: scholar with an index of h has published h papers
each of which has been cited by others at least h times
G-index
• Egghe concept: scholar with an index of g has published g papers
which altogether have been cited by others at least g2 times
Impact factor
• average number of citations received per paper published
in that journal during the two preceding years
* Lane J. Nature 464: 488-9 (2010)
Why Publish Scientific Papers?
For the field:
• Transparent and open exchange of ideas
• Credit for simultaneous or disputed discoveries
For the publisher:
Sir Isaac Newton
• Since 17th century, most scientific journals published by
scientific societies
• Now: > 2000 publishers
• Reed Elsevier, Springer Science and Business Media, and
John Wiley & Sons have 42% of publishing market
• Shrinking university library budgets: books, monographs,
journals, electronic resources
For you (the author/investigator):
Gottfried W. Leibniz
• Communicate your observations and results
• Metric for career advancement/promotion
• Factor in peer-reviewed funding decisions
The Scholarly Paper
What are scholarly publications?
• Contains original research results
(a report or an article)
• Reviews existing research findings
(a review or perspective)
What is the value added by the journal or book?
• Peer review: quality and priority for publication
(process which varies greatly journal to journal,
publisher to publisher, and field to field)
• Safeguard against plagiarism
• Editing
Peabody Library
How is academic publishing
changing?
• More journals (>30,000/yr) and
papers (>1.9 million/yr)
• Movement from print to electronic
format
• Changes in business models for
publishers
• Open access
Great Achievements in Prostate Cancer Treatment
Charles B. Huggins
1966 Nobel Prize in
Physiology or Medicine “for
his discoveries concerning
hormonal treatment of
prostatic cancer”
Patrick C. Walsh Malcom A. Bagshaw
1996 Charles F. Kettering Prize
“for outstanding contributions to
the treatment of cancer”
awarded by the General Motors
Cancer Research Foundation
Huggins C and Hodges CV. Cancer Res 1: 293-7 (1941);
Walsh PC, Lepor H, and Eggleston JC. Prostate 4: 473-85 (1983);
Bagshaw MA, Kaplan HS, and Sagerman RH. Radiology 85: 121-9 (1965)
Plagiarism and Fraud: Increased Risk with
Collaborative Teams?
Study of plagiarism*
•
•
•
•
•
212 pairs of articles with signs of plagiarism
Average text similarity in original article versus duplicate was 86.2%
Average number of shared references was 73.1%
Only 22.2% of the duplicates cited the original article
71.4% of the manuscript pairs shared at least one
highly similar or identical table or figure
• 42% also contained incorrect calculations, data inconsistencies,
and reproduced or manipulated photographs
Plagiarism detection/prevention tools
• eTBlast , Turnitin, iParadigm, CrossCheck,
EVE2, OrCheck, CopyCheck,
and WordCHECK
* Long TC et al. Science 323: 1293-4 (2009)
Sun Z et al. PLoS One 5: e12704 (2010)
MC Escher
Amgen Study of 53 “Landmark” Papers Driving
New Anti-Cancer Drug Development*
Features of Papers with Findings that
Could be versus Could Not be
Reproduced*
Journal
Impact
Factor
Number
of
Articles
Mean Number of
Citations of NonReproduced
Articles
Mean Number of
Citations of
Reproduced
Articles
>20
21
248 (3-800)
231 (82-519)
5-19
32
169 (6-1909)
13 (3-24)
*“Non-reproduced findings” indicated that further anticancer drug development should not be pursued
Collaboration and Team Science
Concluding Thoughts
• Major health problems such as cancer
require urgent solutions
• SKCCC/Johns Hopkins has highly-skilled
faculty members across many fields
• High performance reams can be
constructed with clear rules of behavior,
identified tasks/goals, transparent data,
facilitated interactions, and managed
recognition and reward
• Major barriers to team science arise from
multiple accumulated incentives
constructed to support individual
researchers
Panel Discussion
• Stephen Baylin, M.D.
• Karen Sfanos, Ph.D.
• Bill Nelson, M.D., Ph.D.
• Vasan Yegnasubramanian, M.D., Ph.D.
• Sheila Garrity, J.D., M.P.H., M.B.A. - moderator