computing life

2 searching for genetic treasures

7 the next top protein model 

10 movie mania 

12 sim sickness 

U.S. Department OF 16 integrating biology HeaLtH anD HUman SerVICeS 

national Institutes of Health 

national Institute of General medical Sciences 18 made possible by... 
What is NIGMS? the national Institute of General medical 

Sciences (nIGmS) supports basic research on genes, proteins and 

cells. It also funds studies on fundamental processes such as how 

cells communicate, how our bodies use energy and how we 

respond to medicines. the results of this research increase our 

understanding of life and lay the foundation for advances in the 

diagnosis, treatment and prevention of disease. the Institute’s 

research training programs produce the next generation of 

scientists, and nIGmS has programs to increase the diversity of the 

biomedical and behavioral research workforce. nIGmS supported 

the research of most of the scientists mentioned in this booklet. 

produced by the Office of Communications and public Liaison 

national Institute of General medical Sciences 

national Institutes of Health 

U.S. Department of Health and Human Services 
From text messaging friends to navigating city streets with GPS technology, 

we’re all living the computing life. But 

as we’ve upgraded from snail mail and 

compasses, so too have scientists. 

Computer advances now let researchers quickly search through DNA 

sequences to find gene variations that 

could lead to disease, simulate how flu 

might spread through your school and 

design three­dimensional animations 

of molecules that rival any video game. 

By teaming computers and biology, 

scientists can answer new and old 

questions that could offer insights into 

the fundamental processes that keep 

us alive and make us sick. 

This booklet introduces you to 

just some of the ways that physicists, 

biologists and even artists are computing life. Each section focuses on 

a different research problem, offers 

examples of current scientific projects 

and acquaints you with the people 

conducting the work. You can follow 

the links for online extras and other 

opportunities to learn about—and get 

involved in—this exciting new interdisciplinary field. 
We share: 

70% 

of our genes with 

fruit flies and 

98% 

with chimpanzees and 

99.9% 

with each other. 

Imagine finding a treasure chest that contains all of the precious gems and 

metals ever mined, but you can only lift the lid far enough 

 see the glint of gold and the sparkle of diamonds. 

That’s how some biologists felt not too long ago. 

Advances in computer technology have opened the 

genetic treasure chest all the way, revealing the 

human genome and answering questions about 

diseases, drug treatments and even crimes. 

to

searching for genetic treasures 

National Institute of General Medical Sciences 
 

? 

In 2005, the U.S. Food 

and Drug Administration 

approved a heartfailure drug specifically 

targeted to African 

Americans. Why do 

you think some people 

raised ethical concerns? 

<02|03> computing life | searching for genetic treasures

MEDICINES that work wonders 

for you can be ineffective — or 

even harmful —to others. Why? 

Age, weight, lifestyle and other 

medicines each play a role, but 

so do GENES. 

Scientists use computers to find the 

specific genetic variations that affect the 

way we respond to drugs. this field of 

research is called pharmacogenetics, 

and its goal is to determine the type 

and dose of medicine best suited for 

each individual. 

Geneticist Gary peltz at roche palo 

alto in California leads one research 

team working in this field. His group has 

looked for tiny differences that change 

how mice process, or metabolize, the 

drug warfarin. 

nearly 2 million americans, especially 

those who have heart disease or are 

recovering from major surgery, take 

warfarin to prevent deadly blood clots. 

But warfarin is tricky to prescribe. too 

much causes excessive bleeding and too 

little could allow clots to form. Doctors 

use a careful, trial-and-error approach to 

find the right amount for each person. 

the California researchers pinpointed 

the gene that makes an enzyme the mice 

need to metabolize warfarin. Searching 

with computers, they then found slight 

variations in the gene’s Dna that could 

influence how quickly the animals 

eliminated the drug from their bodies. 

the scientists were able to use the 

mice’s genetic profiles to predict how 

the mice would process the drug. Similar 

studies in humans could ultimately help 

doctors more quickly and precisely 

prescribe the right dose of warfarin. 

>side effects: genes and medicines 

By Susan Gaidos 
> answers from africa 

By Alisa Zapp Machalek 

Geneticist Sarah Tishkoff splits 

her time between her LABORATORY 

at the University of Pennsylvania 

in Philadelphia and remote parts 

of AFRICA. 

She works with and collects Dna from 

people as diverse as hunter-gatherers 

in the jungles of central africa; graingrowing farmers in southern africa; 

and nomadic, cattle-raising warriors 

in eastern africa. 

By designing computer models to 

compare the Dna of these different 

populations, she hopes to track down 

gene variations that make some people 

less susceptible to malaria — one of 

the world’s leading causes of death. 

people in certain african tribes that 

have been exposed to malaria for 

thousands of years can contract the 

disease and survive it. these tribespeople developed genetic adaptations 

that gave them natural resistance to 

malaria, which they passed on to their 

National Institute of General Medical Sciences 

Tishkoff enlists African 

tribespeople in her project 

to understand how human 

genomes have responded 

to malaria. > Sarah Tishkoff 

descendants. through the generations, 

the resistance genes have become more 

common in the population. 

tishkoff calls this process the “footprints 

of natural selection.” Following the trail 

can lead scientists to the genetic basis of 

innate resistance — and possibly to future 

therapies —for malaria and other diseases. 

So far, the trail has taken tishkoff to 

data indicating that innate resistance to 

malaria is caused by a variant in the gene 

for a specific enzyme nicknamed G6pD. 

people with this genetic variant make 

less of the enzyme, which is needed for 

several important chemical reactions 

inside cells. 

Up to one-quarter of the people living 

in malaria-infested regions of africa have 

this variant. everywhere else, fewer than 

5 percent have it. 

Understanding how the G6pD genetic 

variant protects people from malaria 

could eventually help treat and prevent 

the spread of the disease. the work, 

tishkoff adds, is also helping to unravel 

the history of modern humans in africa 

and beyond. 

web exclusives @ http://publications.nigms.nih.gov/computinglife/searching.htm 
 

 

 

 

 

 

 

<04|05> computing life | searching for genetic treasures

>word games
 

If you’re hooked on SUDOkU, you 

should try the letter game called 

GENETIC CODE. Here’s an 

easy example: Put the following 

words in a sequence so that each 

one differs from the previous word 

by just one letter. 

FAN BIT BAT BAN FUN 

now imagine working with words 

that contain thousands of letters. and, 

instead of shuffling around recognizable 

words, you have long, seemingly random 

strings of as, ts, Gs and Cs —the letters 

of the Dna code. 

that’s what scientists face when they 

try to track and analyze changes within 

an organism’s genetic material, or 

genome. the task may sound tough, 

but it’s easy with the help of computers. 

Scientists typically start with a 

collection of gene sequences from 

different people or organisms. these 

sequences could come from blood, 

bodily tissues or even ancient bones. 

to figure out when the variations 

occurred, researchers use computational tools to put the gene sequences 

in chronological order. In this way, 

computers are revealing the genetic 

changes, combinations and quirks that 

create the earth’s remarkable biological 

diversity. — AZM 

>mutiny against antibiotics
 

What can dirty DIAPERS teach us 

about MEDICINE? That infectious 

bugs are cagey. 

When scientists designed the first 

antibiotics more than 50 years ago, 

they called them medical marvels. the 

drugs cured common infections caused 

by bacteria in just days, slashing death 

rates and transforming medical care. 

But through tiny genetic changes, 

prompted in part by our own overuse and 

misuse of antibiotics, super bugs now 

outsmart our once super drugs. Certain 

bacterial strains have developed resistance to antibiotics that once killed them 

and passed this ability to their descendants. today, a few of these strains can 

even overcome every existing antibiotic. 

Scientists thought that after many 

generations without exposure to antibiotics, the bacteria would eventually 

succumb to the drugs once again. 

Unfortunately, that doesn’t seem to be 

the case, says Bruce Levin, a population 

geneticist at emory University in 

atlanta, Georgia. 

Levin analyzed E. coli bacteria —the 

harmless kind in our colons —found in 

70 dirty diapers from a day care center. 

One-quarter of the bacteria in the used 

diapers were resistant to streptomycin, 

an antibiotic rarely prescribed in the 

previous 30 years. 

Levin’s diaper discovery was buoyed 

by research led by richard Lenski, 

a microbiologist at michigan State 

University in east Lansing who trained 

in Levin’s lab. 

Since 1988, Lenski has monitored 

flasks of streptomycin-resistant E. coli. 

after 10 years and 20,000 bacterial 

generations, he flooded the bugs with 

streptomycin for the first time. they 

remained unfazed by the drug. 

Levin and others have run thousands 

of computer simulations to come up 

with strategies that slow the development and spread of resistance. 

make up 

your own 

3-letter series, and 

ask your friends 

to arrange them. 

! 

, FUn. an , F an , B at the answer is: BIt, B

! 

blow 

your nose. 

There’s a good chance 

that your tissue contains 

Staphylococcus aureus, or 

“staph” bacteria. Normally, 

this common bug doesn’t 

cause sickness, but it 

occasionally can be lifethreatening. Computer 

models can help identify 

strategies for keeping the 

spread of these infections 

at bay, especially in 

hospitals, where they can 

be the most dangerous. 

Because drug-resistant bacteria will 

continue to plague us, Levin jokes that 

research on antibiotic resistance offers 

the perfect career opportunity. He says, 

“We must continually discover new ways 

to deal with bacterial infections. I tell 

students that when you graduate from 

school, there are plenty of things for 

you to do!”— AZM 
In 1995, a Louisiana nurse accused 

her ex-boyfriend, a doctor, of attempt

ed MURDER. She claimed he gave her 

the AIDS virus by injecting her with 

blood from an HIV-positive patient. 

Lawyers from both sides recruited 

scientists to analyze viral DNA from 

the nurse. 

to prove its case, the prosecution 

had to convince the jury that the virus 

from the nurse and the virus from the 

patient were close relatives. So, scien

tists dusted for Dna fingerprints! 

the investigative team, led by 

computational biologist David Hillis at 

the University of texas at austin and 

virologist michael metzker at Baylor 

College of medicine in Houston, texas, 

used a technique called Dna fingerprint

ing to compare the Dna sequences from 

the two viral samples. the team also 

used a number of different computer 

programs to piece together how the viral 

sequences most likely changed between 

the alleged injection in 1994 and the trial 

in 1998. 

the results showed that certain 

genetic sequences from the nurse’s virus 

were identical to those of the patient’s 

­

­

­

> csd: crime scene dna 

virus. the doctor was convicted of 

attempted second-degree murder and 

sentenced to 50 years in prison. Lawyers 

appealed his case all the way up to the 

U.S. Supreme Court, which let the 

conviction stand in 2002. 

the case marks the first time that 

such genetic analysis, called phylo

genetics, was used as evidence in a 

U.S. criminal court. — AZM 

­

By 2010, the Innocence Project, 

which offers legal assistance to 

people who claim they’ve been 

wrongfully accused, says that 

DNA fingerprinting had led to the 

freeing of more than 240 people. 

? who do you 

think is guilty? 

Evidence from a crime scene 

leads police to five suspects. 

Compare DNA from the perpetrator’s blood left at the crime scene 

with the suspects’ DNA below. 

DNA sequence from perpetrator’s 

blood found at the crime scene: 

AGGCTGCCTACGCGGTTAGG 

DNA sequences from suspects: 

#1 AGGATGGCTACCCGGTTAGG 

#2 AGGCTGCCTCAGCGGATAGG 

#3 AGGCTGCCTACGCGGTTAGG 

#4 CGGCAGCCTACTCGGTTAGG 

#5 AGGCTGGATACGCGGCTAGG 

In the Louisiana murder trial, 

scientists compared more than 

2,000 letters of HIV from about 30 

people. Computers did most of 

the work! 

Computational biologists 

helped prove that a doctor 

tried to murder his exgirlfriend using a syringe 

filled with the AIDS virus. 

National Institute of General Medical Sciences 

the answer is: #3. 
<06|07> computing life | the next top protein model

­

Baker used his computer program 

to design a small protein not found 

in nature. > Brian Kuhlman, Gautam Dantas, David Baker 

the next top protein model 

From building muscles to healing wounds, our bodies rely on proteins — chains 

of small molecules called amino acids that fold into unique shapes. Incorrectly 

folded proteins can cause disorders like sickle cell disease or cystic fibrosis. 

Ever-improving computer power is making it easier for researchers to 

predict how proteins fold and interact with other molecules, possibly leading 

to new treatments for protein-related disorders. 

> tailor-made proteins 

By Emily Carlson 

Scientists can easily determine the three-dimensional shape 

a protein’s amino acid sequence, of his made-up molecule. 

but they can’t reliably PREDICT Baker used that sequence to 

build an actual protein that was how this sequence will fold into stable and quite similar in struc a three-dimensional STRUCTURE. ture to the one he had drawn, 

So computational biologist David validating his approach. Baker at the University of Washington With the ability to whip up new in Seattle took a different approach. He proteins, Baker’s research may make started by sketching a protein structure it possible to customize proteins that that nobody had ever seen. next, he could be used as drugs or tiny biological relied on a computer modeling program machines to treat certain diseases. 

he developed called rosetta to tell him 

what amino acid sequence would form 

web exclusives @ http://publications.nigms.nih.gov/computinglife/topprotein.htm
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

National Institute of General Medical Sciences 

>modeling@home 

In high school, Johnathon Tinsley 

had MIXED feelings about MATH and 

SCIENCE. “Math was very challenging,” he recalls. “I enjoyed some 

parts of biology, but not physics.” 

this British teenager helped 

search for cures for diseases like 

aIDS and alzheimer’s just by 

letting researchers use 

his computer when he 

wasn’t. You can get 

involved, too! 

tinsley is part of 

a tech trend called 

distributed computing 

that relies on the public 

to help advance health 

and medicine. through this 

approach, researchers harness 

the power of personal computers to 

WARNING! 

Before you download 

distributed computing 

software onto a public 

computer, like the ones at 

school or work, ask if it’s 

OK. If you don’t, you could 

get into serious trouble! 

DC Distributed computing 

@home Most likely a distributed computing project 

Credit Points received for solving a calculation 

Work Unit Problem sent to a donated computer 

BOINC The Berkeley Open Infrastructure for Network 

Computing, or the free software program used 

by many DC projects 

PC Personal computer 

Server Computer that sends information to other 

computers in a network 

Wanna Volunteer? 

Folding@Home: http://folding.stanford.edu 

Rosetta@home: http://boinc.bakerlab.org/rosetta 

FightAIDS@Home: http://fightaidsathome.scripps.edu 

If you visit the Web sites of distributed 

computing projects, you’ll likely find 

computerese. Here’s a brief glossary. 

While you’re sleeping, your 

computer could be doing 

scientific research. 

answer important questions about biology. 

the typical computers in a scientist’s lab 

can’t perform all of the required number 

crunching, but a network of hundreds and 

even thousands of personal computers can. 

How It Works 

You join a distributed computing network 

by downloading free software. 

When your computer isn’t busy, 

it sends a message to a server 

in the researcher’s lab 

basically saying, “Hey, I’m 

available. Can I help?” the 

server assigns a chunk of a 

large calculation that it knows 

the home computer can solve. 

the donated computer may 

spend several days working out 

the problem. When it’s done, it hands 

in the answer. Just like teachers, people 

in the lab check the result, also making 

sure that no one has tampered with 

the information. 

You can volunteer your computer, 

whatever the make or model. the computer must be connected to the Internet— 

the type of connection doesn’t matter. 

Older computers can do the job, although 

they generally get simpler calculations. 

You can also choose how much computer 

memory you want to donate. 

You don’t need to worry about hackers 

breaking into your computer system. 

Security checks protecting the main 

servers and the limited capabilities of the 

required software make participating in 

the projects considerably safer than 

surfing the Internet. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

<08|09> computing life | the next top protein model

Distributed Computing 

in Action 

“the science we can do is unmatched by 

what we could do with any other available tools,” says Vijay pande, a scientist 

at Stanford University in California who 

started a distributed computing project 

called Folding@Home. 

pande studies the dynamics of how 

proteins fold into their unique shapes. 

By studying how they fold, pande can 

see what goes wrong and how drugs 

might patch misfolded proteins. 

proteins fold much faster than you can 

fold a shirt. the quickest one is done in just 

5 millionths of a second. 

pande says that it would take a very 

fast desktop computer more than a 

thousand years to completely simulate 

the process! But with the help of nearly 

250,000 personal computers and more 

>project structure
 

Most people enjoy a little friendly 

COMPETITION, and protein structure prediction researchers are no 

exception. Every other year, these 

experts go head-to-head to see 

whose computer MODELS make 

the best predictions. 

the goal is to most accurately model 

the shapes of pre-selected proteins. the 

contestants don’t know the actual structures of these molecules, but the judges 

do. after reviewing the entries, the judges 

invite the most successful modelers to 

an international meeting where they talk 

about the approaches they used. the 

entire group discusses how all can do 

an even better job in the future. 

than 1 million playStation® 3 gaming 

consoles, pande can do the job in less 

than a week. 

tinsley donated about 40 hours of 

processing time every day between 

his two computers. He liked knowing 

that his computers were doing something useful. tinsley says, “they’re 

not just sitting there like stuffed 

lemons”— British slang for being idle. 

For his distributed computing projects, tinsley tracked how much work 

his computer contributed compared to 

others’. If his computer helped predict 

a protein structure, he saw his name on 

the project’s Web site and maybe even 

published in a scientific journal. Some 

projects also would award special 

certificates. 

“Seeing the impact makes a big 

difference,” says pande. “When you 

the scientists don’t actually call the 

event a “contest” or even a “competition.” 

It’s a “community-wide experiment” to 

improve the accuracy of protein prediction 

modeling so researchers can discover 

new drugs more quickly and cheaply. — EC 

donate to many charities, you don’t see 

a direct link between what you give and 

how it’s used. For us, you can actually 

see what your computer has donated and 

the results.” 

Serving science, though, is not the only 

benefit. Distributing computing also offers 

its participants an active social network. 

many projects have message boards 

where donors can post questions about 

the science or random thoughts about life. 

Donors who really want to be ranked at 

the top often will form competitive teams. 

“I like competing to get my stats 

above my team members’,” says tinsley. 

But he also has enjoyed the social 

aspect. For one team, he explains, “the 

main aim is to meet and talk with friends 

and do something good and worthwhile 

while we’re at it.”— EC 

Scientists often are 

rewarded for making 

big breakthroughs, with 

the Nobel Prize being 

the ultimate honor. 

Read about the winner 

of a high school science 

competition on page 18. 

The computer model 

generated by David 

Baker’s team for the 

2004 community-wide 

experiment (left) was 

strikingly similar to the 

protein’s actual structure 

(right). > philip Bradley, David Baker 
 

 

 

 

 

 

 

 

National Institute of General Medical Sciences 

movie mania 

Just as sound and color revolutionized the film industry, computer technology 

has changed the way scientists view biology. Researchers today not only 

can take snapshots of 

biology, they can animate 

entire biological processes, 

thrusting viewers deep into 

never-before-seen worlds. 

>scientists develop sixth sense
 

Thanks to a HIGH-TECH tool, scientists 

just regained their “SIXTH SENSE.” 

Before you think of a certain flick 

starring Bruce Willis, think about feeling 

your muscles flex as you push a box 

across carpet or plunging forward as 

your car suddenly stops. these physical 

responses to external cues are what 

many experts consider the 

sixth type of sensory 

experience. 

A scientist manipulates plastic 

models of two proteins while 

the computer tracks and 

displays their electrostatic 

properties, shown here as 

red and blue clouds. > arthur Olson 

Some scientists 

lost this sense in the 

computer age. they no 

longer used physical models of biological molecules, like proteins or Dna, to 

see how they fit together. Instead, they 

used computer-generated models. 

“many scientists stopped working 

with physical models altogether,” says 

arthur Olson, a structural molecular 

biologist. “the nature of spatial perception changes and the kind of understanding you get from interacting with your 

surroundings were lost when computer 

graphics took over.” 

Olson and his team at the Scripps 

research Institute in La Jolla, California, 

have developed a tool that allows them 

to do both: physically 

manipulate a model of 

a biological molecule 

while watching its 

chemical and biophysical properties change 

on a computer screen. 

Olson says combining 

the two experiences 

will let researchers approach and 

understand biological problems in 

new ways. 

the scientists use special printers 

that generate plastic or plaster 3-D 

shapes as easily as other printers 

produce 2-D pictures. as Olson and 

others hold and interact with the models, 

a camera records a close-up shot of the 

models in motion. a computer program 

then superimposes graphics, like the 

arrangement of atoms or the energy 

between modeled molecules. 

Olson combines the model and 

computer graphics into one image that 

allows him to study all the different facets 

of the biological molecule. Olson hopes 

that one day his interface could double as 

a video game that lets students explore 

and play at the molecular level. — EC 

! pick up 

a nearby object. 

Rotate it so you see all 

its sides. Does it feel 

heavy? What about cold? 

Smooth? How would you 

determine these qualities 

if you only saw the object 

on a computer screen? 
 

 

 

 

 

 

<10|11> computing life | movie mania

>now playing on a computer near you
 By David Bochner 

Superman is super strong, super 

fast and generally super fly. But in a 

COMIC book, he’s also super FLAT, 

leaving many of his superhero feats 

up to your imagination. But when 

the comic book turns cinematic, 

Superman truly comes ALIVE. 

Sometimes scientists only get to 

see the comic book view of biology: 

experimental data gives researchers just 

snapshots of what a biological process 

looks like at a specific time. So, computational biologist Kevin Sanbonmatsu at the 

Los alamos national Laboratory in new 

mexico is bringing those processes to life. 

Sanbonmatsu uses high-performance 

computers to create movies of a tiny 

molecular machine present in every 

living organism. this machine — called 

the ribosome — builds proteins from the 

genetic instructions encoded in Dna. 

The ribosome plays itself in this molecular 

movie, now appearing on the Computing Life 

Web site. > Kevin Sanbonmatsu 

Interested in understanding the origin 

of life, Sanbonmatsu says he studies the 

ribosome because “it may be the oldest 

artifact in the cell.” 

But there’s more to it than curiosity. 

Sanbonmatsu also says that about half 

of all antibiotics used to treat bacterial 

infections target the ribosome, meaning 

that a better understanding of this biological 

machine could lead to super-strong drugs. 

to make his movies, Sanbonmatsu 

starts with experimental data, like the 

structure of a ribosome in a particular 

instance, and generates a storyboard of 

sorts. Hundreds of connected computer 

processors — or a supercomputer—then 

turn the snapshots into an entire movie 

filled with information scientists couldn’t 

otherwise see or even imagine. 

“You can look at static structures of 

the ribosome,” says Sanbonmatsu, “but 

the only way to watch it in motion is the 

supercomputer simulation.” 

His team has created one of the 

largest biological simulations ever, 

bringing new life to characters in the 

old story of protein synthesis. 

An artist’s rendering of how chemicals change and move among cells in 

the brain. Watch the animation on the Computing Life Web site. > Kim Hager 

Amid a network of BLOOD vessels 

and star-shaped support cells, 

neurons in the BRAIN signal each 

other. The mists of COLOR show the 

flow of important molecules, such as 

glucose, oxygen and nitric oxide. 

this image is a snapshot from a 

52-second simulation created by Kim 

Hager, an animation artist working with the

Laboratory of neuro Imaging at the 

University of California, Los angeles. the

animation, which portrays how chemicals 

change and move among cells in the brain,

took about 300 hours to create. to put it 

all together, Hager worked closely with 

neal prakash, a neurobiologist in the 

same lab. prakash initially asked for a 

> the art of animation 

By Karin Jegalian 

drawing to illustrate a research paper, but 

the director of the lab suggested produc

ing an animation instead. 

Hager, who studied photography, video 

and graphic design in college and later 

earned a graduate degree in media arts, 

does not draw movies frame-by-frame. 

Instead, she builds “virtual sculptures” 

filled with color, light, texture and motion 

and then guides the viewer’s eye through 

the scenes. 

­

the lab features this animation, along 

with dozens of others, on its Web site and 

also plays it in a state-of-the-art theater 

during presentations for scientists, 

students and other visitors. 

Hager says her role is to make the 

research more accessible to different 

audiences. “Seeing an animation,” she 

explains, “makes it easier to comprehend 

what a researcher is saying.” 

web exclusives @ http://publications.nigms.nih.gov/computinglife/moviemania.htm
National Institute of General Medical Sciences 

> preparing for a pandemic

MIDAS, 

not to be confused with 

the king who turned 

everything to gold, stands 

for Models of Infectious 

Disease Agent Study. 

? How would your simulated life be different 

from your best friend’s? 

Just months after the first cases of Flu and You 

, to create the pandemic flu simulations, 

the mIDaS researchers use computer 

models to build virtual cities, countries 

and even continents. Here, 

thousands of pretend people 

go to school, work, stores 

and other places. the 

researchers base the 

residents’ activities on 

information about actual 

people like you. 

Stephen eubank, a 

physicist at Virginia tech 

University in Blacksburg and part of the 

mIDaS team, has modeled virtual 

versions of major 

U.S. metropolitan areas using local 

transportation and census data. In 

eubank’s cities, there really are six (or 

fewer) degrees of separation between 

any two people — making it easy for 

germs to spread. 

“Viruses don’t care much about 

geography,” says eubank. “they care 

about social networks and how people 

come into contact with each other.” 

SWINE FLU appeared in April 2009

millions of Americans had gotten 

sick and some had even died. 

By the end of the year, the 

virus had spread world

wide, creating the first 

influenza PANDEMIC 

since 1968. 

as drug companies 

produced a vaccine that 

prevented millions more from 

catching this flu, researchers 

participating in an international project 

called mIDaS were simulating disease 

spread. the simulations let them explore

how the pandemic might unfold, who 

was more likely to get sick and which 

interventions might protect the most 

people. the results helped inform public

policy decisions. 

­

sim sickness 

Scientists are creating their own virtual worlds where people live and work— 

and get sick. Here, researchers can mimic viruses and predict the spread of 

contagious diseases through a community. Successful simulations can help us 

better prepare for real-life outbreaks. 
 

 

 

 

 

 

 

 

 

 

 

<12|13> computing life | sim sickness

type a search word into GoogleTM and 

Meet the Simulators 

Stephen Eubank started out 

studying high-energy physics 

but then got into modeling the 

dynamics of nonlinear systems, 

which are systems that can’t be 

solved by adding up all of the 

parts. He has developed computational models to study natural 

languages, traffic patterns and 

financial markets. He plans to use 

the infectious disease models to 

study how behaviors, like smoking, 

spread through society. 

Christina Mills has a Sc.D. (like a 

Ph.D.) and an M.D. For her, modeling infectious diseases is a dream 

job because it combines her 

interests in math, biology and 

human health. While most of her 

colleagues with double degrees 

practice “bench-to-bedside” 

research in which they translate 

lab findings into patient care, 

Mills says she’ll stick with the 

“computers-to-clinics” approach. 

? What questions 

would you want 

to ask the models? 

simulate a 180-day outbreak in a matter 

Virtual Viruses 

another key part of studying the spread 

of infection with computers involves 

developing a virtual version of the germ. 

to model its spread as realistically as 

possible, the researchers track down 

everything known about the infectious 

agent. eubank, who has studied plague, 

smallpox and anthrax, has gathered 

information on how each agent spreads 

between people, how contagious it is 

and how long it takes for an infected 

person to show symptoms. 

When they don’t know the actual 

characteristics of an infectious disease, 

the mIDaS researchers use health 

reports and scientific data collected 

during earlier outbreaks to estimate what 

a future one might be like. 

During graduate school, Christina 

mills modeled a pandemic flu before we 

had ever heard of swine flu (also called 

H1n1). She did a lot of her research 

in the library, scouring the shelves for 

scientific articles that discussed the 

1918 Spanish flu —a pandemic that 

killed between 20 and 40 million 

people worldwide. 

“It was very old-fashioned,” says 

mills, who was studying international 

health at Harvard medical School in 

Boston, massachusetts. “I couldn’t just 

get the necessary information.” the 

hunt eventually led her to the 1918 

transmission rates. 

Asking Questions 

With all the modeling pieces in place, the 

mIDaS researchers invite policymakers 

to ask questions that can be answered 

using the models. Questions range from 

What happens if we don’t do anything? 

to How many people could be protected 

if we intervene? 

the researchers create different 

simulations that change the variables, 

like the contagiousness of the virus or the 

number of people taking “snow days”— 

eubank’s term for people who voluntarily 

hang out at home to avoid infection. 

“What’s so great about the computer 

simulations is that you can try out 

different situations that you can’t 

create in real societies,” says eubank. 

With more than 250 possible combinations to simulate, eubank says he 

relies on statisticians to help him 

determine which arrangements will 

produce the most informative results. 

“It’s easy to come up with questions,” 

says mills. “the hard part is figuring 

out which ones we should — and 

could — answer.” 

Because of the amount of data and 

calculations involved, the simulations run 

on high-performance computers that can 

of hours. eubank uses software programs to take snapshots of the pretend 

pandemic as it occurs. 

“I know exactly when a virtual person 

gets infected, shows symptoms and 

recovers,” says eubank, explaining that 

the computer records every change in 

disease state. 

>>>
In 2006, MIDAS modelers mapped the potential spread 

of pandemic flu in the United States. Each dot changes 

from green to red as more people in that area get sick. 

The top map shows what could happen if we didn’t 

do anything. The bottom map shows the effect of 

giving people a less effective vaccine while a better 

one is being developed. > Proceedings of the National Academy of Sciences 

Watch this pandemic flu spread on the Computing Life 

Web site. 

National Institute of General Medical Sciences 

Flu Forecast 

eubank and other researchers 

modeling the 2009 H1n1 pandemic 

flu simulated outbreak scenarios in 

communities across the United 

States. the results suggested that 

early vaccination of school kids best 

reduced disease spread, while 

vaccinating elders became more 

important later on. the simulations 

also indicated that people at risk for 

serious complications—like pregnant 

women or individuals with preexisting health problems—should be 

given antiviral medicines to take at 

the first signs of illness. 

While the results generated by 

the simulations are useful, eubank 

stresses that they’re not a guarantee 

of what actually will happen. He and 

others often will ask different models 

the same questions and, when the 

models agree, they’ll have more 

confidence in the predictions. — EC 

! create a timeline 

of what you did yesterday. 

List all the people (even if 

you don’t know their names) 

you came into contact with. 

If you were contagious with 

the seasonal flu, how many 

of these people do you think 

you would have infected? The 

answer is surprisingly low. 

Estimates suggest that you’d 

pass the virus to no more than 

three people. But if more than 

one other person catches it 

from you, the bug will continue to spread. 

web exclusives @ http://publications.nigms.nih.gov/computinglife/simsickness.htm
 

 

 

 

 

 

 

virus actually causes its own 

demise. Like a hungry wolf pack 

that clears out the local deer 

population, the virus eventually 

starves itself. Infecting too many 

people reduces its “food” 

supply. 

this work is just one example 

of how researchers can develop 

models to answer questions 

about outbreaks of dengue 

or other diseases. With a math

ematically based model, ecologist 

pejman rohani at the University of 

Georgia in atlanta examined 30 years of 

epidemiological data from thailand, a hot 

spot for dengue. He learned that envi

ronmental factors, like warmer 

temperatures, can re-route mosquito 

flyways and in turn change dengue 

infection rates. 

­

­

<14|15> computing life | sim sickness 

>the rise & fall of deadly dengue
 

This map from 2007 shows areas infested with the 

mosquito that carries the dengue virus (orange) and 

areas with both the mosquito and dengue epidemic 

activity (red). > Centers for Disease Control and prevention 

Dengue is common 

in Haiti, and survivors of the massive 

earthquake that 

devastated the country’s capital in 2010 

faced a greater risk 

of infection due to 

standing water and 

contaminated sanitation systems. 

By Alison Davis 

If you live in the United States and 

don’t travel ABROAD, chances 

are you’ll never come down with 

DENGUE fever. That’s not the case 

for people living in tropical and 

subtropical climates, like South 

America, Africa and the Caribbean. 

Between 50 and 100 million of these 

people catch the mosquito-transmitted 

dengue virus every year. most of them 

will bounce back after 2 weeks of rest 

and extra fluids. a small percentage, 

however, won’t be so lucky. after 

contracting dengue a second time, 

some people may develop a potentially 

fatal dengue hemorrhagic fever. 

Scientists suspected that the human 

immune system might be to blame for 

making the second infection more 

dangerous, but until recently they 

weren’t sure how. 

Using computer simulations, 

epidemiologists at the Johns Hopkins 

Bloomberg School of public Health in 

Baltimore, maryland, learned that the 

infected person’s antibodies — proteins 

that should fight off dengue — actually 

help the virus copy itself. more copies 

make the virus a better predator, 

allowing it to spread faster and infect 

more people. 

But the researchers—Derek 

Cummings and Donald Burke, who is 

now at the University of pittsburgh in 

pennsylvania—also learned that the 
 

 

 

 

 

 

 

integrating biology 

> bacteria blast off 

Identifying all the parts of a cell or organism won’t necessarily tell you how 

those parts work together to make the system run. To do this, scientists 

have turned to a relatively new field called systems biology that combines 

experimental data and computational models to diagram everything from 

how cells move to how hearts beat. With the diagrams, the researchers can 

tinker with different parts and begin to explore questions nearly impossible 

to answer through traditional lab experiments. 

National Institute of General Medical Sciences 

Ten, nine, eight, seven, six, five, four, 

three, two, one . . . BLAST OFF! 

While this object might look like a 

rocket blasting through space, it’s really a 

fake bacterium jetting around a virtual cell. 

It represents Listeria, a type of bacteria 

best known for causing food poisoning. 

Computational biologist Jonathan 

alberts and mathematical biologist 

Garrett Odell at the University of 

Washington’s Center for Cell Dynamics 

in Friday Harbor created it to study how 

the bacterium moves around the cells 

it infects, ultimately making you sick to 

your stomach. 

By combining experimental data 

with computer-based approaches, 

alberts and Odell have created virtual 

models of Listeria that show it moving 

through time. this more complete 

picture may enable the researchers to 

identify new ways to prevent foodborne illnesses. — AD 

In this computer model, a Listeria bacterium propels itself through an infected 

cell by stimulating the growth of cellular filaments (yellow and red) at the 

cell’s surface. > Jonathan alberts, Susanne rafelski, Garrett Odell 

web exclusives @ http://publications.nigms.nih.gov/computinglife/integratingbiology.htm 
Each spot on this globe represents a 

city, and each color corresponds to a 

community of easily connected cities. 

> Luis a.n. amaral, roger Guimerà 

This sphere represents all the known 

chemical reactions in the E. coli 

bacterium. > Luis a.n. amaral 

 

 

 

 

 

<16|17> computing life | integrating biology

Like us, CELLS rely on transporta

tion to do their daily activities. But 

while we can choose to take cars, 

busses, bikes and even Segways® , 

cells take the pedestrian approach

They MOVE themselves. 

a cell moves by grabbing onto 

something, like the wall of a blood 

vessel, and then pulling itself forward. 

this mobility is an essential part of 

wound healing. When you cut yourself, 

your white blood cells speed to the 

wound like paramedics. 

But cellular movement can also cause 

health problems, like when cancer cells 

spread to other parts of the body. 

Scientists want to understand how 

cells move so they can develop new 

­

> on the move

drugs that can rev up or stop cell migra biology approach to studying cell 

tion altogether. But like most biological movement. She uses mathematical 

processes, cell movement hasn’t been equations and computer software to 

: easy to figure out because it involves piece together the various component

hundreds of proteins. that make cells motor along. — AD 

Cell biologist Clare Waterman-Storer 

at the national Institutes of Health in 

Bethesda, maryland, takes a systems 

­

s 

? Did you know that 

some cells form ladders 

so other cells can climb 

up them? 

This image, taken with a microscopecamera, shows the intricate network of 

fibers that builds a cell’s structure. These 

fibers are called microtubules (yellow) and 

actin filaments (blue). > Clare Waterman-Storer 

>connected worlds
 

For scientists, the INTERNET is 

more than an information superhighway and AIRPORTS aren’t just 

places where planes take off and 

land. They are examples of complex 

NETWORkS that can help researchers study even more complicated 

ones in the body. 

networks, whether social or cellular, 

share a number of features. each one is 

a system made up of different elements 

that connect through important centers 

of activity called hubs. Hubs could be 

Web pages linked to many other sites or 

major airports that route passengers to 

additional cities. Communication occurs 

within the network, letting it organize 

itself and even change over time. 

any network can serve as a model for 

understanding another because all these 

systems operate by a similar set of rules, 

says physicist Luis amaral at northwestern 

University in evanston, Illinois. 

amaral models the networks of the 

Internet and air travel, but he also maps 

metabolic networks — the intricate 

pathways by which cells generate the 

energy needed to carry out biological 

processes spanning the production of 

proteins to the breakdown of drugs. He 

creates simple computational models that 

show how the paths of these complicated 

networks connect and communicate. 

Knowing all the details about the body’s 

networks may help scientists learn to rewire them to prevent certain diseases, just 

like air traffic controllers re-route planes to 

avoid thunderstorms. — AD 
 

 

National Institute of General Medical Sciences 

made possible by... 

You’ve learned a lot about how computing power gives us new perspectives 

on biology. At the center of it all is a component more advanced than 

any silicon chip inside a computer processor. It’s the human brain. 

Biologists, engineers, physicists, computer scientists, 

epidemiologists, geneticists and even writers and 

artists have brought their brainpower to the 

table to solve these old and new problems. 

>time for computation 

By Jilliene Mitchell 

Going from Mom’s or Dad’s savory that predicts how proteins fold and attach algebra course, he says he knew it was 

home cooking to the CAMPUS to other biological molecules. time to visit the math help room, where 

By the time he graduated from high students could work with tutors. the effort cafeteria’s “mystery meat” can be school, Harrison had presented his paid off. Harrison finished the class with a a big adjustment for any COLLEGE research to scientists older than his B-, which, considering how tough the class freshman. But for Ryan Harrison, a parents and received numerous awards, was, he says felt more like an a+. 

BIOMEDICAL engineering and including a top prize in the 2005 Intel “I study a lot,” admits Harrison. “But I 

economics major at Johns Hopkins Science talent Search — the nation’s still make time to do things that I enjoy.” 

University in Baltimore, Maryland, it oldest and most prestigious high among his hobbies: directing a onewasn’t a big deal. school science competition. act play, experimenting with light and 

While most of his high school friends after graduation, Harrison sound for student theater productions and 

returned to Hopkins and playing his favorite computer game. took it easy their last year to fully enjoy 

the Gray lab. even nd he taught disadvantaged kids “senioritis,” Harrison spent his downtime 

with a full college in Baltimore how to play chess, at Hopkins, where he worked in the 

course load, he explaining that it was also good chemical and biomolecular engineering 

still found time to practice for him. lab of professor Jeff Gray. Harrison got 

work on rosetta. With so many interests, one the chance through his high school, 

which offers a program that pairs Don’t be of Harrison’s biggest challenges 

fooled, though. in college was finding time for 

all of his activities — and 

deciding what he ultimately 

wanted to do professionally. as 

he wrote in his online diary (see 

excerpts on the next page), “I have 

more questions now about my 

future than ever before. But, I 

guess that’s ... a normal part of 

growing up.” 

students with researchers. 

Just because he Harrison had been writing his own 

was an award- computer programs since the 4th grade. 

winning researcher So when his high school biology teacher 

at age 17 doesn’t introduced him to Gray, everything fell into 

mean he’s a whiz place. “He was into computational biology 

at everything! When and we immediately hit it off!” says Harrison. 

While he started losing the in the Gray lab, Harrison 

battle in a high-level improved the rosetta computer program 

Harrison in high 

school, when 

many scientists 

mistook him for a 

college or graduate 

student! 

> Stephen Spartana 

a
 

 

<18|19> computing life | made possible by...

> excerpts from an internship
 

Ryan Harrison spent his first 

SUMMER off from college in New 

York City, where he did a 10-week 

INTERNSHIP at Weill Medical 

College of Cornell University. 

Instead of working in a computer 

lab, he worked in a “wet lab,” complete 

with live organisms, chemicals and petri 

dishes. He studied how a particular 

protein affects the life cycle of the 

parasite that causes malaria. 

Harrison wrote about his summer 

experience in his blog, “Verdant Force: 

Discoveries in Life and proteomics.” 

B L O G 

NAME: 

Ryan 

Harrison 

Thursday 8:37pm 

“I’ve been in New York City for almost a month now. 

Settling in well to my new lab environment and even 

forgetting that I’m in NYC occasionally. . . . Wish I 

could work a little more independently, but I understand that I just don’t have the proper laboratory 

background/experience to handle my own independent project. I guess I was expecting a Gray lab type 

arrangement— where I work at my own pace at a 

problem I selected and I am the only one responsible for the outcome (good or bad). . . . Whatever I 

decide to do, I think it will combine computational 

with “wet lab” work. Since I haven’t the slightest 

idea how my life is going to unfold, I am just going 

to do what I enjoy.” 

To find out what Harrison is doing now, 

visit this story on the Computing Life Web site. 

Drew Endy likes taking things APART What got you interested in science? Why do you want to do this? 

and putting them back together — I’m curious. It bothers me when I don’t I started to think about why it’s been so 

bikes, cars, lawn mowers. He understand how things work. hard to understand biology. the conclusion 

I’ve come to is that the biological systems essentially does the same thing You’re trained as an engineer. How does 

we find in nature aren’t easy to understand. when he tries to understand that influence your approach to biology? 

I figure that if I want to have biology that If you ask engineers what they want to BIOLOGY. A professor at Stanford I understand, I’d be better off building do in their heart, they want to make University in Palo Alto, California, it myself. something. my interest is to be able to Endy assembles and PROGRAMS routinely, reliably, quickly, easily and What makes the field so hot right now? 

living machines. I asked him a few cheaply put together the bits and pieces Seventy years ago, physicists came 

questions about his work and why of biology to make new and useful things. into biology and really shook things up. 

he likes it. — DB I suspect that what’s happening now is You’re in a new field called synthetic 

that the engineers are coming into biology, biology. What’s the goal of this field? 

and they’re going to shake things up. It’s to make routine the engineering — 

the programming — of living organisms. 

> programming biology

>>> 

web exclusives @ http://publications.nigms.nih.gov/computinglife/madepossible.htm
National Institute of General Medical Sciences 

With the help of a Hollywood illustrator and others, Endy created a comic book called 

Adventures in Synthetic Biology. He hopes to use it as a teaching tool. To read the 

entire comic, visit this story online. > Drew endy

 Describe your typical day.

 I feel like I’m an enzyme, helping stuff 

happen. I teach courses on synthetic 

biology, and I supervise the research in my 

lab. every now and then I get a little bit of 

time to think. 

What have you thought about lately? 

are we discovering biology faster or 

slower than nature is inventing new biology? 

I did some back-of-the-envelope calculations, 

and this number could be completely wrong, 

but sometime between the year 2085 and 

2105 we should be able to sequence all the 

Dna on the planet in a month. 

 What do you like most about your job? 

the people in research are some of the 

coolest, [most] interesting [and] nicest 

people you’re ever going to meet. It’s just 

a great experience. 

What do you think makes for a 

successful scientist? 

the best, most fun-loving, happy 

scientists I’ve seen are the people who 

recognize when an idea isn’t working and 

abandon it for a better idea without feeling 

too bad. 

Do you think you’ll always be a scientist? 

I’m doing what I want to be doing, and if 

I wasn’t, I would change it. If at some point 

in the future, I’d rather be raising pheas

ants in southern France, or northern 

France, or wherever they raise pheasants 

in France, I presume I would go do that. 

Of course, I’d have to learn French.

 Last words? 

people express great wonderment, 

excitement and almost a magical relation

ship with the living world. But I think over 

the coming years —faster than most 

expect— we’ll see a transition in biology 

where it becomes much simpler and 

easier to engineer living systems. We don’t 

actually know how to do that right now, 

but there are lessons buried in the lore and 

wisdom of other engineering disciplines. 

­

­
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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publications.nigms.nih.gov/computinglife. 
 

 

 

 

 

 

“When I was in high school, I never thought there 

was a field that combined all my interests.” 

— Christina Mills, a scientist who uses modeling to study 

infectious diseases 

> think you want to compute life?
 

People with many different talents 

can join in COMPUTING LIFE. If you’re 

interested, ask yourself what aspects 

of the research featured here you find 

EXCITING. Do the projects blend many 

of your academic interests? Are there 

particular biological problems you’d 

like to solve? 

Here are a few tips on how to get 

started looking into COMPUTING LIFE 

as a career. 

nIH publication no. 10-5861 

February 2010 

http://www.nigms.nih.gov 

Read, Share, Recycle. 

> ask your science teacher or 

guidance counselor about 

opportunities to work with a 

researcher at a nearby college 

or other institution. 

> Search the Web for scientists 

working at the crossroads of biology 

and computation. 

> e-mail scientists at your local 

college or university for more 

information. 

> enter a science fair to get experience presenting research results.