Emerging Researchers National Conference in STEM, Washington DC, Feb 20, 2015

1. Biomedicine – from
Stethoscope to Computer
Philip E. Bourne
NIH Associate Director for Data Science
Emerging Researchers National Conference in STEM
February 20, 2015

2. What I do…
I run a program at the NIH which supports projects that
advance the contribution of the computational and
quantitative sciences to biomedical discovery.
I also run a research lab at the NIH where we do
computational biology with an emphasis on
protein structure.

3. How I think I got here…
• I embrace change
• I make and keep lots of friends and
colleagues
• I keep questioning assumptions
• I follow my heart
• I learned to live with regret
• I try to make the most of every day
• I go after the big problems
• I give back to the scientific community and
society
Google “PLOS Ten Simple Rules”

4. The Life of One Scientist – The Early Years
So That You Might Not Make the Same Mistakes
• My high school
teacher Mr. Wilson
said I would be a
failure at chemistry
• My PhD is in
chemistry
• The opportunity to live
in different places
shaped my life
• Good friends are forever

5. PhD in
Physical
Chemistr
y

6. Always Loved Computing
Circa 1974

7. Postdoctoral Work – The Molecular
Basis of How the Body Works
• Regrets: never learnt another
language

8. Post Doc

9. Some Things Stay with You Your Whole
Life
9

10. Senior Scientist HHMI Columbia
University New York
• Driven not by career but wanting to
live in New York City

11. ~1990 Got Involved with
The Human Genome
• Was only possible by
applying computers to
problems in biology
• Developed algorithms to
support physical and
genetic mapping of
Chromosome 13

12. Went to UCSD to Apply Computers to
Big Biological Problems
In 1993 possibly the best place
in the world to do
computational biology

13. Eventually…. I Fell in Love with the
Data Problem

14. Numberofreleasedentries
Year
The Growth of Data is A Major Driver
in Biology

15. Realized that there is still more
work for me to do… it isn’t all in the
lab… and it is in Washington, D.C.
New Job!
Associate Director for Data
Science (ADDS)
at the National Institutes of
Health (NIH)
Mission: To accelerate
and support the integration
of the computational and
quantitative sciences and
the biomedical sciences.
I also got to move my lab to the NIH – my group’s research in
protein structure biology continues here in the D.C. area and with
collaborations all over the world.

16. WHAT MOTIVATES ME TODAY?
3 VIGNETTES

17. 1. Josh Sommer and Chordoma
Disease
http://fora.tv/2010/04/23/Sage_Commons_Josh_Sommer_Chordoma_Foundation#fullprogram

18. Josh Sommer – A Remarkable Young Man
Co-founder & Executive Director the Chordoma Foundation
http://sagecongress.org/Presentations/Sommer.pdf

19. Chordoma
• A rare form of brain
cancer
• No known drugs
• Treatment – surgical
resection followed by
intense radiation
therapy
http://upload.wikimedia.org/wikipedia/commons/2/2b/Chordoma.JPG

20. http://sagecongress.org/Presentations/Sommer.pdf

21. http://sagecongress.org/Presentations/Sommer.pdf

22. http://sagecongress.org/Presentations/Sommer.pdf

23. http://sagecongress.org/Presentations/Sommer.pdf

24. http://sagecongress.org/Presentations/Sommer.pdf

25. http://fora.tv/2010/04/23/Sage_Commons_Josh_Sommer_Chordoma_Foundation

26. Open Data leads to faster cures
Collaboration
• Open Data generates collaborations and supports Team
Science
• Collaborations bring in more researchers
Big Data
• More researchers create more data
• More researchers create different types of data
Faster Cures
• Computational Science helps biologists do more with all
that Big Data
• Big Data leads to new discoveries.

27. Drug Discovery

28. The Worst of Times
Source: http://www.pharmafocusasia.com/strategy/drug_discovery_india_force_to_reckon.htm

29. Here is One Reason Why
• Tykerb – Breast cancer
• Gleevac – Leukemia, GI
cancers
• Nexavar – Kidney and liver
cancer
• Staurosporine – natural product
– alkaloid – uses many e.g.,
antifungal antihypertensive
Collins and Workman 2006 Nature Chemical Biology 2 689-700

30. Bioinformatics – Reverse Engineering
Drug Discovery
Characterize ligand binding
site of primary target
(Geometric Potential)
Identify off-targets by ligand
binding site similarity
(Sequence order independent
profile-profile alignment)
Extract known drugs
or inhibitors of the
primary and/or off-targets
Search for similar
small molecules
Dock molecules to both
primary and off-targets
Statistics analysis
of docking score
correlations
…
Xie and Bourne 2009
Bioinformatics 25(12) 305-312

31. 2. HARNESSING SOCIETY FOR
SCIENCE
A Team of scientists is great but….what if ordinary people could
help us do science. Computer games are the key.

32. Nature’s Reductionism
There are ~ 20300 possible proteins
>>>> all the atoms in the Universe
11.2M protein sequences from
10,854 species (source RefSeq)
38,221 protein structures
yield 1195 domain folds (SCOP 1.75)

33. Bridging fields to support
innovationSometimes biomedical research is mind-numbingly
BORING! How can we manage time-intensive, low-skill
tasks without biologist burn out??? Crowdsourcing?

34. Research Games for Citizen
Science

35. Think Tank: Game Developers and
Biomedical Researchers
9 biomedical researchers
&
10 game developers
December 9-10, 2014 @
NIH
To address challenges of how these two communities
collaborate, exchange data science & visualization
expertise, and develop games for enabling and
performing biomedical research

36. 3. PRECISION MEDICINE
For the first time in history health care is patient centric.

37. President Obama’s State of the
Union Address: January 20, 2015

38. “And that’s why we’re here today. Because something
called precision medicine … gives us one of the greatest
opportunities for new medical breakthroughs that we
have ever seen.”
President Barack Obama
January 30, 2015

39. EHRsPatient Partnerships
Data Science
GenomicsTechnologies

40. www.nih.gov/precisionmedicine

41. Precision Medicine
Concept is not new
• Consider prescription eyeglasses, blood transfusions…
• Prospects for broader application raised by recent advances
in basic research, technology development, genomics,
proteomics, metabolomics, EMRs, Big Data, mHealth, etc.
• Reinforced by 2011 National Research Council report
What is needed now
• Development of rigorous research program to provide
scientific evidence needed to turn concept into reality
• Recruitment of the best and brightest from multiple disciplines
to join the team

42. Precision Medicine Initiative:
The Time Is Right
Ten Years Ago
Now – 2014
(most recent data)
Cost of sequencing a
human genome
$22,000,000 $1000 - $5000
Amount of Time to
Sequence a Human
Genome
2 years <1 day
Number of smart
phones in the United
States
1 million (<2%) 160 million (58%)
EMR Adoption,
(% providers)
20-30% >90%
Computing Power n n x 16

43. Precision Medicine:
What Success Might Look Like
50-year-old woman with type 2 diabetes
visits her doctor
• Now
– Though woman’s glucose control has been
suboptimal, doctor renews her prescription for
drug often used for type 2 diabetes
– Continues to monitor blood glucose with
fingersticks and glucometer, despite
dissatisfaction with these methods

44. Precision Medicine:
What Success Might Look Like
50-year-old woman with type 2 diabetes visits her
doctor
• Future: + 2 years
– Volunteers for new national research network
• Sample of her DNA, along with her health information, sent to
researchers for sequencing/analysis
• Can view her health/research data via smartphone
– Agrees to researchers’ request to track her glucose
levels via tiny implantable chip that sends wireless
signals to her watch, researchers’ computers
• Using these data, she changes diet, medicine dose schedule

45. Other Diseases:
What Success Might Look Like
50-year-old woman with type 2 diabetes
visits her doctor
• Future: + 5 years
– Receives word from her doctor about a new
drug based upon improved molecular
understanding of type 2 diabetes
– When she enters drug’s name into her
smartphone’s Rx app, her genomic data
show she’ll metabolize the drug slowly
• Her doctor alters the dose accordingly

46. Other Diseases:
What Success Might Look Like
50-year-old woman with type 2 diabetes visits
her doctor
• Future: + 10 years
– Celebrates her 60th birthday and reflects with her
family about how proud she is to be part of cohort
study
– Her glucose levels remain well controlled; she’s
suffered no diabetes-related complications
– Her children decide to volunteer for cohort study

47. NIH… Turning Discovery Into Health
@pebournephilip.bourne@nih.gov