Biomedicine from Stethoscope to Computer

Biomedicine – from

Stethoscope to Computer

Philip E. Bourne

NIH Associate Director for Data Science

Emerging Researchers National Conference in STEM

February 20, 2015

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.

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”

The Life of One Scientist – The Early YearsSo 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

PhD in

Physical

Chemistr

y

Always Loved Computing

Circa 1974

Postdoctoral Work – The Molecular Basis of How the Body Works

• Regrets: never learnt another language

Post Doc

Some Things Stay with You Your Whole Life

9

Senior Scientist HHMI Columbia University New York

• Driven not by career but wanting to live in New York City

~1990 Got Involved withThe Human Genome

• Was only possible by applying computers to problems in biology

• Developed algorithms to support physical and genetic mapping of Chromosome 13

Went to UCSD to Apply Computers to Big Biological Problems

In 1993 possibly the best place in the world to do computational biology

Eventually…. I Fell in Love with the

Data Problem

Num

ber

of

rele

ased e

ntr

ies

Year

The Growth of Data is A Major Driver in Biology

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.

WHAT MOTIVATES ME TODAY?

3 VIGNETTES

1. Josh Sommer and Chordoma

Disease

http://fora.tv/2010/04/23/Sage_Commons_Josh_Sommer_Chordoma_Foundation#fullprogram

Josh Sommer – A Remarkable Young Man

Co-founder & Executive Director the Chordoma Foundation

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

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

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

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

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

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

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

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

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.

Drug Discovery

The Worst of Times

Source: http://www.pharmafocusasia.com/strategy/drug_discovery_india_force_to_reckon.htm

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

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

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.

Nature’s ReductionismThere 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)

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?

Research Games for Citizen

Science

Think Tank: Game Developers and

Biomedical Researchers

9 biomedical researchers &

10 game developersDecember 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

3. PRECISION MEDICINE

For the first time in history health care is patient centric.

President Obama’s State of the

Union Address: January 20, 2015

“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 ObamaJanuary 30, 2015

EHRsPatient Partnerships

Data Science

GenomicsTechnologies

www.nih.gov/precisionmedicine

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

Precision Medicine Initiative:

The Time Is Right

Ten Years AgoNow – 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

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

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

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

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

NIH… Turning Discovery Into Health

@[email protected]