Professional Documents
Culture Documents
Genes To Galaxies Astrobiology
Genes To Galaxies Astrobiology
100 km
Low Lunar Orbit
Direct or Skip Entry
Land Landing
Service
Module
Jettison
Low
Earth
Orbit
Vehicles Not
to Scale ale
A
R
E
S
I
,
A
R
E
S
V
160
|
Genes to Galaxies
via a docking tunnel, but inhabits Orion until
reaching low lunar orbit (LLO). Once in LLO,
the crew places Orion into a quiescent state
and enters Altair for the descent to the lunar
surface. Orion continues orbiting the moon,
passing over the landing location of Altair ap-
proximately every two hours, for the duration
of the lunar surface stay. During this time,
Orion generally serves as a communication
relay for Altair if the Earth is out of view from
the surface, and also performs regular rocket
burns to maintain a stable orbit. Once the
crews stay reaches duration, they ascend into
orbit with Altair, rendezvous, re-dock with and
enter Orion, and then jettison the Altair ascent
vehicle before returning home.
For the reentry, descent and landing phase
of the mission, one of the most critical and
intense phases even compared to the landing
on the moon, Orion utilizes one of the largest
thermal protection systems (heatshield) ever
designed at fve meters in diameter. Much of
the heatshield material ablates away due to
extremely high temperatures of 2,600 C dur-
ing the time Orion decelerates through the at-
mosphere from an initial entry speed of nearly
11 kilometers per second. Unlike the Shuttle,
Orion does not utilize wings and therefore
does not perform runway landings. Instead,
a sequence of two drogue parachutes triggers
the deployment of three giant main chutes to
slow the spacecraft to a cushy splashdown of 7
meters per second in the ocean.
Orions command module resembles the Apollo
command module in that the shape is a blunt-
body cone capable of withstanding the ex-
tremely high heating experienced during Earth
reentry. It is the habitable portion of the Orion
vehicle. The service module provides capabili-
ties necessary during the mission, such as the
engine used to return from LLO to Earth and
consumables like water, and is jettisoned prior
to reentry. The vehicle confguration at launch
also incorporates a launch abort rocket system
to rapidly whisk the capsule away from the
launch vehicle in the unlikely event of a rocket
mishap on the launch pad or during ascent.
For electrical power, Orion relies on two radial
solar arrays that each span fve meters across.
Therefore, Orions orientation with respect to
the sun at any given time is extremely criti-
cal for the health of the vehicle. Exposure to
micrometeoroids, orbital debris, and radiation
increases with longer mission durations, sub-
sequently increasing the robustness required of
the array design.
Orions internal space, known as habitable vol-
ume, is extremely limited due to limitations on
the weight and dimensions the Ares 1 design
is capable of launching. The spacecraft interior
contains 2.5 times the space of the Apollo cap-
sule, but for twice as many astronauts. With a
Figure 3: Orion vehicle in low earth orbit with solar arrays deployed.
NASA/John Frassanito & Associates
New Stars in NASAs Constellation
|
161
volume of 11 cubic meters, each crewmember
has limited personal space to eat and drink,
let alone take a shower. (Imagine a room three
meters long and two meters square, about the
size of a large sport utility vehicle.) The Space
Shuttle might seem luxurious comparatively
where the astronauts currently enjoy a private
bathroom, as opposed to Orions solution of
using a small curtain to separate the toilet
area from the rest of the crew. Tomorrows
astronauts must be prepared for close quarters,
albeit for only a few days!
Altair
Altair, also known simply as the lunar lander,
provides the capability to take four astronauts
and any necessary payload from LLO down
to almost any location on the moons surface.
Unfortunately, Altair has limited capacity for
payloads due to the space required to house
the crew and other life support logistics such
as breathing systems, water, and space suits. In
order to build an outpost on the moon requir-
ing living and working quarters, as well as large
mobility robots, it is necessary to have a way
to carry much heavier payloads than normally
possible in the presence of crew. Therefore,
Altair is being designed with three possible
confguration variants:
short-duration crewed variant a seven-day 1.
exploratory mission where Altair provides all
life support logistics necessary
long-duration outpost variant an extended 2.
mission of up to 210 days where Altair pro-
vides the way down to the surface and back
into orbit, and an outpost is expected to sus-
tain the crew for the duration
cargo-only variant crew quarters and life 3.
support are stripped out to maximize the
amount of cargo (over 14 metric tons) that
can be delivered
For a crewed mission, Altair launches from
Earth on an Ares V, mates with the Orion in
LEO, and then undergoes a functional check-
out by the crew to verify proper operations of
critical systems such as life support, power, and
guidance. Following the three-day journey to
the moon, Altair is responsible for providing
the propulsion for it and Orion on at least three
major rocket burns resulting in close to 4,200
meters per second of total velocity change or
delta V. The frst burn takes the Orion and
Altair vehicles out of the trans-lunar trajectory
and places them in an orbit around the moon
at approximately 100 kilometers in altitude.
At this point, the crew transfers out of their
cramped Orion home into a more cramped
Altair home to prepare for their fnal hours
before landing. Prior to descent, a short burn
Figure 4: Orion and Altair in a mated confguration on the way to the moon prior to lunar
orbit insertion. NASA/John Frassanito & Associates
162
|
Genes to Galaxies
to adjust the orbit plane may be necessary to
fne-tune the targeting to the landing site, and
fnal system checks are completed before com-
mitting to the fnal powered descent burn.
Over 60% of Altairs mass consists of propellant
to carry out the mission.
The current Altair design is equipped with a
large cryogenic liquid oxygen and hydrogen
(LOX/LH
2
) main descent propulsion system,
and a smaller hypergolic reaction control
system that burns monomethyl hydrazine and
nitrogen textroxide (MMH/NTO) propellant.
These small thrusters provide thrust for minor
attitude corrections to Altair and Orion when
mated, as well as small, planned burns that are
ineffcient for the main engine.
The signifcant diffculty of using cryogenic
propellant for the main engine lies in the
mission duration and the propellants low
saturation temperature for the designated tank
pressure. Current launch systems utilizing
cryogenic fuels typically perform a single burn
almost immediately after lift-off that is complet-
ed in less than 20 minutes. In contrast, Altairs
trip to the moon takes a minimum of 4 days
from the time of lift-off, and extreme challenges
exist in keeping the propellant suffciently cold
to prevent loss due to boil off. After landing on
the moon, residual propellants feed a fuel cell,
Altairs primary power source. That need for
power, and possibly water as a fuel cell reaction
by-product, is expected to last up to 210 days.
If managing the cryogenic propellants for an
extended period of time presents technical
challenges, one might wonder why we use
them. For a quick transit to the moon, cryo-
genics provide an extremely high specifc im-
pulse. The consequence is that the propellant
is extremely effcient in terms of energy release
potential per unit mass. Other types, includ-
ing choices with easier thermal management
requirements, would be less mass effcient and
therefore result in the need to carry more pro-
pellant to perform the same job. Such a mass
increase would potentially result in a vehicle
prohibitively heavy to fy.
For a cargo mission, Altair launches from Earth
and transits directly to the moon without dock-
ing with an Orion capsule. By not requiring
time in orbit to transfer crew and supplies, a
cargo Altair can execute a simpler orbit initia-
tion sequence to position itself for a direct
landing and avoid orbiting the moon alto-
gether. In order to accomplish this autonomous
landing, Altair relies on intelligent sensors and/
Figure 5: Altair accompanied by three crewmembers in an artists conception of what a
sortie mission might look like on the l`unar surface.
Image courtesy NASA/John Frassanito & Associates
New Stars in NASAs Constellation
|
163
or pre-placed beacons in order to touch down
on the lunar surface, while avoiding major
rocks, craters, and other hazardous obstacles
placed in its path. This capability becomes
extremely critical when trying to land multiple
Altairs within a kilometer or less of one another
during the outpost construction campaign.
The Apollo landings all took place during
lunar noon and in the equatorial region. The
lighting allowed them to see rocks and craters
during descent more easily than if they had
encountered long shadows caused by landing
at a time with the sun near the moons hori-
zon. Apollo missions also landed in relatively
smooth terrain known as Mare. These loca-
tions allowed the astronauts to aim for rela-
tively large landing zones with low probabilities
of steep craters or large rocks. Due to the
Constellation goal of exploring a more diverse
set of regions on the moon, Altair will face situ-
ations that may put it in darkly lit, or rough re-
gions known as hummocky uplands, with cra-
ters as wide as 295 kilometers (crater Bailly)
and as deep as 8.8 kilometers (Newton).
There are several potential technologies that
Altair and the crew might employ for safe land-
ing. One specifc solution might be in design
confict with another, so determining the right
combination of those solutions is challenging.
A stronger structure may withstand impact
from hazards or higher loads at landing, but
can add prohibitive amounts of mass. A softer
landing, or one that allows the vehicle to
maneuver away from hazards in real-time, typi-
cally results in carrying more fuel and requiring
tightly constrained control of the vehicle. Better
sensors result in easier detection of hazards,
but rely on more costly computer processing
hardware and algorithm development. There
are many different sensor options currently
under consideration that could aid Altair and
its crew in knowing its position relative to
landmarks, helping it to line up with maps of
the surface generated by orbiting satellites, or
Figure 6: Exploded view of the Ares I
vehicle with Orion in its position at launch.
Image courtesy NASA/John Frassanito & Associates
164
|
Genes to Galaxies
identifying and avoiding hazards in real-time
once within a few kilometers of the surface.
NASAs Lunar Reconnaissance Orbiter
(LRO) and Indias frst mission to the moon,
Chandrayaan-1, are among two of the robotic
lunar orbiter missions that are providing topo-
logical data to assist the Constellation program
in choosing landing sites for Altair. The qual-
ity of the data and amount of coverage help
determine the robustness of Altairs landing
capability required to safely touch down at the
selected sites. Chandrayaan-1 will also focus on
performing high resolution mineralogical and
chemical imaging in shadowed polar regions
as well as searching for surface or sub-surface
water-ice. This data will inform scientists as to
the highly desired landing locations based on
scientifc merit versus vehicle capability to land
in challenging terrain.
Once on the surface, Altair either provides life
support and habitat functions as mentioned
previously, or sits dormant during the crews
stay at the outpost. At the conclusion of the
surface mission, Altairs ascent vehicle, the
same module utilized by the crew during
descent, will blast off and head for low lunar
orbit. The bottom portion of the vehicle, con-
sisting of the descent engine, empty fuel tanks,
and landing gear, serves as a launch pad for the
ascent vehicle and is left behind on the lunar
surface. For this part of the mission, Altair
utilizes an engine and propulsion system de-
signed specifcally for the ascent to lunar orbit
and rendezvous with Orion. After rendezvous
and docking, the crew then transfers back into
Orion through the hatch and prepares for re-
turn to Earth. Prior to the trip home, the crew
commands Orion to jettison Altair and places
it on a trajectory to minimize interference with
future missions.
Ares I and Ares V
Because a combined launch of both vehicles is
mass prohibitive for a single rocket, and Altair
weighs almost twice as much as Orion, each
spacecraft warrants its own launch vehicle.
Both Orions and Altairs boosters draw from
existing technologies where feasible, but new
capabilities are also being developed. Orion
utilizes a design called the Ares I. This rocket,
currently under development at the Marshall
Space Flight Center in Huntsville, Alabama, is
a thin, 99-meter tall vehicle capable of lifting
25 metric tons to LEO. The Ares I frst stage
is a single, fve-segment, reusable solid rocket
booster derived from the Space Shuttle pro-
grams reusable solid rocket motor. It separates
133 seconds after launch and is recovered from
the Atlantic Ocean and reused. The upper stage
employs a liquid fueled engine derived from
the original Saturn Vs J-2, and burns for 495
seconds to take Orion to an altitude of 134
Figure 7: The Ares V approximately 6 seconds after ignition as it lifts from the launch
pad at Cape Kennedy. Image courtesy NASA/John Frassanito & Associates
New Stars in NASAs Constellation
|
165
kilometers. After separation from the upper
stage, Orion boosts itself into a circular orbit
while the upper stage reenters the atmosphere
and plunges into the Indian Ocean.
In contrast to Orion, Altair utilizes the giant
Ares V booster. Prior to the Constellation effort,
the largest and most powerful rocket ever built
was the Saturn V for the Apollo Program. The
three-stage Saturn, an engineering marvel of
the 1960s, stood 111 meters high and utilized
fve F-1 engines to produce greater than 33
million Newtons of thrust for the frst stage. It
boasted a LEO payload capability of 344 metric
tons. The Ares V is a two-stage liquid-fueled
rocket that stands two meters shorter than the
Saturn V, but is still taller than the length of a
soccer feld. This rocket is capable of boosting
414 metric tons to LEO. It relies on two reus-
able solid rocket boosters, similar in design
to the Ares I frst stage, which strap onto the
sides to assist a frst stage powered by six RS-
68B engines. The second stage, referred to as
the Earth Departure Stage (EDS), performs the
trans-lunar insertion burn for the mated Orion-
Altair vehicle. This maneuver transitions the
spacecraft from an Earth orbit to a path that
will intersect the Moon.
In looking ahead at a Mars capability, the Ares
V is being designed such that additional solid
rocket boosters can be adjoined providing ad-
ditional lift capacity for heavier spacecraft.
Surface Systems
The technologies to sustain life on the moon
and beyond are in the earliest stages of devel-
opment, but already have some very exciting
prototypes under test in exotic locales such as
the Mojave Desert and Antarctica. One element
of living on the moon is mobility, both for
people and objects such as science experiments
and living quarters. The moon, while much
smaller than the Earth, is still a large place to
Figure 8: An exploded view of the Ares
V with Altair in its launch position. The
Earth Departure Stage (EDS) can be seen
below Altair.
Image courtesy NASA/John Frassanito & Associates
166
|
Genes to Galaxies
Figure 10: The
enclosed rover
concept being
tested in the
Arizona desert.
The rover shares
the shared chassis
of the chariot
concept.
Image courtesy NASA
Desert RATS team
Figure 9: An
evening test run
of the NASA-
prototyped
chariot concept
in the Arizona
desert.
Image courtesy NASA
Desert RATS team
explore. The Apollo astronauts walked around
in spacesuits, and used their open air lunar
rover to explore up to a few kilometers from
the landing site. Constellation astronauts can
also perform walking excursions near the land-
ing location, but a small enclosed rover is being
designed to provide a shirt-sleeve environment
for two crew to live for days at a time while
driving 20 to 30 kilometers away from the
habitat location. Todays rover concept is a six-
legged vehicle with 12 wheels. The prototype
was recently taken out to the Arizona desert
where engineers tested it to understand its
maneuverability, obstacle avoidance capability,
and ease of controllability.
Similar to the enclosed rover, the design of the
habitats and workspaces is challenging due the
New Stars in NASAs Constellation
|
167
constraint of landing them on a limited-size
vehicle such as Altair. They require packaging
that occupies as little space and mass as possi-
ble. Engineers are currently working on designs
that collapse around a central, rigid core and
infate or expand once on the surface. Multiple
modules can be connected together through
common airlock doors, including a hatch to
pull up and park the enclosed rover when not
in use. The scalability of designs is a key factor
due to the fexibility of designing either one
module to meet all needs, or the luxury of uti-
lizing several specifc modules. Radiation and
micrometeoroid hazard robustness also affect
habitat design, providing an opportunity for
material specialists to develop unique, light-
weight methods to provide protection.
These large modules dictate the need for the
ability to unload large, heavy objects down
from the top of Altairs deck, a height equiva-
lent to a three-story ledge. Once removed from
the deck, astronauts will need to transport the
modules over rocks, craters, and other pieces
of unloaded hardware before reaching the fnal
destination. ATHLETE, the All-Terrain Hex-
Legged Extra-Terrestrial Explorer, is another
lunar surface concept being designed to do just
that. It utilizes jointed, six-degree-of-freedom
limbs to help it crawl on and off of the Altair,
maneuver next to an Altair to help with repairs
or resource retrieval, or align two habitats for
proper connection to increase living and work
space. Both remote control and autonomous
operations are currently being tested to allow
a crewmember to operate it while remaining
within the relatively safe confnes of an estab-
lished outpost, or perform other work while
the ATHLETE accomplishes its tasks.
Human suit design is also a large part of the
Constellation effort. Engineers are working to
design astronaut surface suits less bulky than
the Apollo units, while more adept at provid-
ing a healthy, safe environment, and capable
of reporting diagnostics of the crew members
health. Certain aspects of the suit may assist an
astronaut in performing strenuous tasks such as
lifting heavy objects, or facilitating exercise by
providing muscular resistance. Another team
is looking at the types of ancillary telemetry to
collect, and effcient display techniques such
as using a heads-up display when an astronaut
is out working. For example, if a crewmember
is out exploring and their rover encounters a
problem, the presence of an internal guidance
and map capability could help them get home.
In addition to the habitat, suit, and mobility
technologies, there exist other surface capabili-
ties under development to facilitate communi-
cations, to extract natural resources found on
the moon, and to increase the autonomy de-
sired of robots. It is also important that aspects
of the spacecraft design employ the concept of
reusability because of the diffculty in landing
material on the moon. For example, potential
components include power sources, water
and fuel processing and storage hardware, and
avionics boxes suitable for both Altair and
reuse at the outpost after the conclusion of the
Altair mission.
In addition to all of the scientifc and engineer-
ing discovery, it is desired that as many of us
here on Earth share in the experiences of the
astronauts on the moon. In order to accomplish
this goal, NASA plans to beam back high-
defnition video so that we can be involved
with the work of the astronauts, and explore
alongside them!
Whats so exciting
about the moon?
In 1969, when our frst Apollo mission landed
two astronauts on the moon, it was an engi-
neering feat of a lifetime. After the upset of
losing the race to the Soviet Union for the
frst satellite in orbit, and the frst human to
orbit and return to Earth, the United States
placed humans on another celestial body.
Unfortunately, the scientifc enlightenment
and excitement of exploring a heavenly locale
that was all but an impossible dream for many
millennia of human history, was cut short after
only six short missions.
Our reasons for going to the moon in 1969
were very different from what they are today.
There is no longer a space race, no Cold War,
no need to be the frst to accomplish putting
a human on the moon. However, what has
not changed is our desire to continue learning
168
|
Genes to Galaxies
about and exploring the universe that waits
outside of our comfortable, earthly bubble.
Many nations have spent substantial time, ef-
fort, and resources exploring our solar system,
including Venus, Mars, and the moons of
Saturn and Jupiter. We have telescopes that see
far beyond what many of us ever thought ex-
isted. Searching for Earth-like planets or gravi-
tational waves beyond our solar system provide
an understanding of our universes origins.
We continue to be excited and intrigued by
tales told via Star Trek and 2001: A Space
Odyssey, which says something about our
capacity and yearning for exploration. In ad-
dition, the Moon provides a unique place to
study our universes origins due to the lack
of changes compared to Earth and the other
planets. The lunar surface has been much less
affected than the Earth by forces of erosion
such as plate tectonics, volcanism, and wind
and water. Consequently, much of the original
formation is more intact than any other known
body we can currently study.
Learning how to survive and be productive on
the moon, a short 363,000 kilometers away,
places us one step closer to traveling to more
distant bodies such as Mars. We can experi-
ment with different concepts of transport, logis-
tics, construction, in-situ resource utilization,
and different communication schemes that may
require inhabitants to operate independent
from Earth for a period of time, or advance our
technology solutions that simply enable us to
survive in a non-earthlike environment. For
example, we have learned a signifcant amount
about how microgravity affects humans physi-
ologically. Mars gravity is slightly stronger than
the moons at 3/8 that of the Earth. By under-
standing the effects of 1/6-Earth lunar gravity
on humans over extended periods of time, we
can better prepare the proper training, exercise
regimens, and diet to mitigate the effects of
Mars gravity.
Conclusion
Sending robotic missions to far away places is
signifcant to learning a great deal about the
basics of a planet or comet, but in order to
perform more in-depth science that requires
real-time decision making and adaptation, we
need the capability to explore frst hand. To
accomplish this imperative, we must invest
in and establish our knowledge of how to live
and operate safely in harsh environments. The
moon provides an excellent opportunity by
being relatively close to home, but still posing
challenging problems in all aspects of the mis-
sion. Can you imagine producing your own
oxygen for breathing, out of soil? How can we
create or bring resources that are reusable or
recyclable into something useful again? What
kind of telescope is best for placement in a
shadowed crater such that it can accomplish
radio astronomy without interference from
the Earth?
While the Constellation program has estab-
lished a plan to fulfll the American space
policy of going to the moon and beyond, it has
not done so in a vacuum. The effort required
for developing and sustaining the capability to
function in a permanent way beyond our Earth
home is promoting numerous international
partnerships between both old space-faring
foes such as the United States and Russia, and
newcomers just getting started. Those such as
Japan and the European Union are increasing
contributors to our knowledge and under-
standing of the universe. This exploration effort
also draws on many different groups of people
as we consider how to build a thriving com-
munity that ultimately needs teachers, doctors,
engineers, scientists and other citizens. Also
thanks to the efforts of independent enter-
prises, almost anyone will have the opportunity
to personally participate in exploration of the
moon during this lifetime.
NASAs effort to renew and establish a capability
for human exploration on the moon is an excit-
ing frontier for many reasons. Constellations
success depends on national and international
support, as well as the success of its many
New Stars in NASAs Constellation
|
169
projects such as Orion and Altair to fulfll their
missions. And, back to the moon we go, but
not just for the moons sake; for the sake of the
moon, Mars, and beyond.
References and Good Resources
National Aeronautics and Space Administration
(NASA). The Vision for Space Exploration. NP-
2004-01-334-HQ. NASA. Washington D.C.
National Academy of Sciences. The Scientifc
Context for Exploration of the Moon National
Academies Press. 2007. Washington D. C.
Latest Constellation News including test vid-
eos, pictures and information: http://www.nasa.
gov/mission_pages/constellation/main/index.
html
Testing surface in-situ technologies in Hawaii:
http://www.nasa.gov/directorates/esmd/home/
hawaii_lunar_tests.html
Information about Shackleton Crater:
http://www.esa.int/esaMI/SMART-1/
SEMP7QOFHTE_0.html
Saturn V Information: http://www.daviddarling.
info/encyclopedia/S/Saturn_rocket.html
Moon Crater Resource: http://museumvictoria.
com.au/DiscoveryCentre/Infosheets/Planets/
The-Moon/
Asthma
and Airway
Remodelling:
Targeting Mitogen-activated Protein
Kinases as Future Therapeutics
Melanie Manetsch
Emma E. Ramsay
Alaina J. Ammit
A
sthma is a chronic disorder of
the airways affecting millions of
people worldwide. Airways are
remodelled, or thickened, result-
ing in airway obstruction and a decline in lung
function. Airway remodelling is considered
to be a consequence of long-term infamma-
tion. As the current drugs for treating airway
remodelling have side effects, we urgently
need to target the infammatory pathways that
control the development of the remodelled
phenotype in the airway. A wealth of studies
has implicated the mitogen-activated protein
kinase (MAPK) family of phosphoproteins as
critical signalling molecules that drive pro-
infammatory pathways. Thus, inhibition of
MAPKs has emerged as an attractive strategy
for reversing infammation and remodelling
in asthma. This chapter will focus on target-
ing MAPKs as future therapeutics. We will
briefy outline the use of small molecule MAPK
inhibitors, and then explore the potential of
harnessing the power of an endogenous MAPK
deactivator MAPK phosphatase 1 (MKP-1)
in inhibiting MAPK-mediated pro-remodelling
172
|
Genes to Galaxies
functions. Our recent studies demonstrate that
MKP-1 deactivates MAPK signalling in airway
smooth muscle cells; a pivotal airway cell in
asthma and airway remodelling. Thus, this
chapter will focus on the role of MAPKs in the
development of the pro-remodelling phenotype
in asthma and highlight the promise of novel
anti-infammatory strategies designed to reverse
the development of the airway remodelling
phenotype by regulating the anti-infammatory
protein MKP-1.
What is asthma?
If you have asthma, you experience episodes
of wheezing, chest tightness and shortness of
breath in response to a variety of triggers.
This occurs because the airways in your lungs
narrow, making it more diffcult for air to get
through. Over 2.2 million Australians have
asthma. This includes 1 in 4 children, 1 in 7
teenagers and 1 in 10 adults (Source: National
Asthma Campaign). Because when you cant
breathe, nothing else matters (American Lung
Association), asthma is an important and de-
bilitating disease that we need to understand
more about so that we can beat it!
What causes asthma?
Asthma is a complex disease with both ge-
netic and environmental causes. Why do we
get asthma? The causes are many and varied.
Allergy may play a big role. According to the
National Asthma Campaign, 8 in 10 Australians
with asthma have positive allergy test results.
Allergy occurs when your immune system
reacts to substances (known as allergens) in the
environment that do not bother most people.
These allergens can be found in house dust
mites, pets, pollen, moulds and foods and
can trigger asthma. You may be born with
a genetic tendency to develop allergic dis-
eases (called atopy); or allergy may develop
throughout life. There are still a large number
of unanswered questions about the develop-
ment of allergic disease but currently much
intense research is being performed all around
the world to understand more about the links
between allergic disease and asthma.
What is the cellular
basis of asthma?
Asthma is characterized by infammation
and airway hyper-responsiveness. An acute
asthma attack can be brought on by exposure
to triggers. Exposure to triggers induces air-
way infammation characterized by mast cell
degranulation and an infux of lymphocytes
and eosinophils. These cells secrete various
agents capable of perpetuating infammation
and provoking airway smooth muscle contrac-
tion (bronchospasm). Accordingly, the majority
of therapeutic agents used for asthma seek to
minimize the development or consequences
of airway infammation (corticosteroids) or
directly promote airway smooth muscle relaxa-
tion (
2
-agonists).
What is airway remodelling?
Asthma is a treatable health condition and we
have a number of effective drug treatments
to tackle acute asthmatic attacks. With good
asthma management, asthmatics can lead nor-
mal, active lives. But, there are still a number of
unanswered questions. We now know that the
airways of asthmatics can become thickened
or remodelled over time. This occurs when the
infammation that is part of an acute asthmatic
attack is not treated or controlled effectively.
The consequence of uncontrolled asthma is
that permanent changes in the airways can
occur and unfortunately, these cannot be
completely reversed with current treatments.
As development of remodelled airways is cor-
related with deterioration of lung function,
we urgently require therapies that reduce
and reverse structural changes in remodelled
airways. Although corticosteroids can inhibit
some aspects of remodelling, side effects ex-
ist and thus, corticosteroid-sparing strategies
to prevent airway remodelling require further
investigation.
Airway smooth muscle plays an integral role in
acute asthma and airway remodelling
In the Respiratory Research Group at the
University of Sydney we have focussed on the
role of the airway smooth muscle in asthma
and airway remodelling. Airway smooth mus-
cle is no longer viewed simply as a bystander
Asthma and Airway Remodelling
|
173
structural cell passively maintaining the airway
wall integrity and responsible for bronchoc-
onstriction; it has now emerged that airway
smooth muscle plays a critical active role in the
pathogenesis of asthma and airway remodel-
ling. When an acute asthma attack is triggered,
airway smooth muscle is bathed in a wide
variety of infammatory mediators released by
mast cells upon degranulation and by-products
of gene expression from lymphocytes and
eosinophils. The airway smooth muscle then
undergoes a number of important cellular
reactions in response to these stimuli. Cells un-
dergo calciummediated contraction and un-
dergo bronchoconstriction that is typical of an
asthmatic attack. Additionally, a number of im-
portant pro-remodelling genes are activated in
airway smooth muscle cells. The protein prod-
ucts of this gene expression result in increased
cell growth and increased production of pro-
fbrotic proteins. It is this increase in airway
smooth muscle mass (due to both increased
airway smooth muscle cells numbers and also
an increase in the amount of fbrotic proteins
in and around the airway smooth muscle cells)
that is considered to contribute strongly to
the thickening of the airway wall. Because
increased airway wall thickening results in
reduced airway calibre (4), airway remodelling
is a signifcant contributor to the exaggerated
airway narrowing observed in asthmatics. It is
generally considered that airway remodelling is
a consequence of long-term infammation, and
although numerous cell types contribute to air-
way remodelling, the increase in airway smooth
muscle mass has the largest impact on airway
narrowing in asthma (5). Thus, airway smooth
muscle plays an integral role in acute asthma
and chronic airway remodelling and under-
standing the underlying signalling pathways
will allow us to design future drug strategies
for reversing infammation and remodelling in
asthma.
MAPKs - signalling pathways
that drive development
of airway remodelling
Our recent work has highlighted the impor-
tance of the mitogen-activated protein kinase
(MAPK) super family of signalling molecules
in the pro-remodelling functions of airway
smooth muscle cells. There are three members
of the MAPK superfamily: (1) p38 MAPK; (2)
c-Jun N-terminal kinase (JNK); (3) extracellular
signal-regulated kinase (ERK, also known as
p44/p42 or ERK1/ERK2). These enzymes are
involved in the intracellular signal transduction
pathways mediated by a variety of stimuli (in-
cluding cytokines, chemokines, growth factors,
neurotransmitters and environmental stresses,
such as allergens, respiratory viruses and
airborne pollutants). To become activated by
these various signals, the MAPKs pass through
ATP-dependent phosphorylation cascades
that consist of three protein kinases connected
in series. Activation of MAPKs requires dual
phosphorylation at the threonine (Thr) and
tyrosine (Tyr) residues of the Thr-X-Tyr sites in
the activation loop (where X is glutamic acid in
the case of ERKs, proline in JNKs, and glycine
in p38 MAPK). Many important substrates
for MAPKs are transcription factors and after
activation the MAPKs migrate to the nucleus
of the cell and there they phosphorylate di-
verse transcription factors on specifc sites and
therefore control gene expression. In this way,
MAPKs work at the key positions of many
intracellular signalling pathways and regulate
various cellular processes, from gene expres-
sion of pro-fbrotic proteins and infammatory
cytokines, to regulation of proliferative path-
ways by increasing levels of cell cycle proteins
to induce cell growth. A wealth of studies has
implicated the MAPK family of phosphopro-
teins as critical signalling molecules that drive
pro-infammatory pathways. Thus, inhibition
of MAPKs has emerged as an attractive strategy
for reversing infammation and remodelling in
asthma. Thus, MAPKs have emerged as critical
pathways that drive development of airway re-
modelling to signifcantly contribute to asthma
pathophysiology (6, 7)
The Respiratory Research Group at the
University of Sydney has been at the forefront
of discovery of the MAPK pathways respon-
sible for critical pro-remodelling functions in
airway smooth muscle cells, such as: increased
synthetic function, production of cytokines
(8-10) and pro-fbrotic proteins (11-13); and
increased cell growth ((13-16)). We now wish
174
|
Genes to Galaxies
to use our knowledge to aid the future design
of drugs that help tackle the development of
airway remodelling in asthma.
Mitogen-activated protein
kinases (MAPKs) as future
therapeutic targets
As recent research underscores the importance
of the MAPK signalling pathways in key airway
smooth muscle functions that underlie the
development of the remodelled phenotype,
these pathways may be targeted as therapeutic
strategies in the future. As the current drugs
for treating infammation (corticosteroids)
have side effects, we urgently need to target the
infammatory pathways that control the devel-
opment of the remodelling phenotype in the
airway, as this knowledge may yield corticos-
teroid-sparing strategies in the future. In this
chapter we focus on two approaches: frstly, use
of small molecule inhibitors to inhibit MAPK
pathways; and secondly, harnessing the power
of endogenous MAPK deactivators, such as
MAPK phosphatase 1 (MKP-1).
MAPK inhibitors
Recent research has begun to elucidate sig-
nalling pathways responsible for key airway
smooth muscle functions that underlie the
development of the remodelled phenotype
(reviewed in (17)). Of the MAPK super family,
most research in the airway smooth muscle
cell arena has focused on the role of the p38
MAPK- and ERK-mediated pathways. Although
an oversimplifcation, p38 MAPK pathways
are considered responsible for synthetic func-
tion and the secretion of cytokines, while
ERK-mediated pathways dominate in airway
smooth muscle proliferation (reviewed by (18,
19)). JNK has only been investigated somewhat
more recently and has been shown to regulate
cytokine gene expression and protein secretion
(20). Thus, as the importance of the MAPK
pathways in airway smooth muscle cell biol-
ogy and infammatory airway diseases such as
asthma and airway remodelling are emerging,
these pathways may be targeted as therapeutic
strategies in the future.
p38 MAPK: p38 MAPK is activated by an ATP-
dependent dual phosphorylation at Thr180
and Tyr182 residues. Many laboratories around
the world have designed and synthesized small
molecules that block the ATP binding site of
Asthma and Airway Remodelling
|
175
p38 MAPK, yielding a large number of poten-
tial p38 MAPK inhibitors (reviewed in (21,
22)). The prototypical p38 MAPK inhibitor
is SB203580, one of the frst generation p38
inhibitors and widely used as pharmacological
tool to study p38 MAPK pathways. We (9, 10,
23) and others (24, 25) have used SB203580
in vitro to highlight the key role played by
p38 MAPK in secretion of pro-infammatory
cytokines from airway smooth muscle cells (9,
10). The importance of p38 MAPK inhibition
as a pharmacotherapeutic approach in asthma
has been further underscored by demonstra-
tion of reduced pulmonary infammation and
airway hyperreactivity in a mouse model of
asthma (26). In vivo, the use of SB203580 as
an anti-infammatory drug has been obstructed
by its liver toxicity, as the pyridinyl imidazoles
were found to inhibit hepatic cytochrome P450
enzymes (27). Promising anti-infammatory
actions have been observed in an in vivo model
with the p38 MAPK inhibitors SD-282 (28)
and further investigations into non-toxic p38
MAPK inhibitors are currently under intense
investigation worldwide.
ERK: Dual threonine and tyrosine phosphor-
ylations activate both ERKs, at Thr202/Tyr204
for ERK1 and Thr185/Tyr187 for ERK2. MAPK
pathways are activated by dual phosphoryla-
tion by respective upstream activators. For
ERK, the upstream kinase is mitogen-activated
protein kinase, known as MEK. There are a
number of MEK inhibitors such as U0126 and
PD98059. These have been used extensively in
vitro in airway smooth muscle cells to delineate
pro-proliferative pathways. We (15, 29) and
others (30, 31) have demonstrated that ERK-
dependent pathways control growth.
JNK: The JNK phosphorylation sites are
Thr183 and Tyr185. Relatively less is known
about the role of JNK in airway smooth muscle
pro-remodelling functions in vitro, although
airway smooth muscle hyperplasia and infam-
matory cytokine release in mice chronically
exposed to allergens is inhibited by the admin-
istration of SP600125, a JNK inhibitor (32).
MKP-1: what is it?
Cellular function is profoundly affected by both
strength and duration of MAPK activation,
which must be strictly controlled to modulate
functional outcome. This crucial negative
feedback control is achieved by the balanced
interplay between MAPK activation by diverse
environmental and chemical stimuli and the
negative feedback mechanism mediated by pro-
tein phosphatases such as MAPK phosphatases
(MKPs) (33, 34). Several MKPs have been
classifed (34) and in general they all regulate
MAPK activity in a negative feedback mecha-
nism by dephosphorylating the threonine and
the tyrosine residues in the activation loop
Thr-X-Tyr-motif of these signalling enzymes.
Since these phosphatases dephosphorylate both
176
|
Genes to Galaxies
the threonine and the tyrosine residues they
are also called dual-specifcity phosphatases
(DUSPs). Although all MKPs have highly
conserved structural elements they vary in
subcellular localization, substrate specifcity,
tissue distribution and also in their inducibility
by various stimuli. The characteristic structural
elements of MKPs are within all MKPs homo-
logue dual-specifcity phosphatase (DUSP)
domain in the C-terminal half which leads to
the dual dephosphorylation on the threonine
and tyrosine residues of MAPKs, and a MAPK-
binding domain situated in the N-terminal half.
This domain is very important for the quality of
the interaction between MKPs and MAPKs and
therefore plays a crucial role in the regulation
of the enzymatic specifcity (35, 36).
MKP-1, the prototypical member of the MKP
family, is an immediate early gene located in
the nuclear compartment and that means that
its transcription is induced instantly after expo-
sure to diverse stimuli such as growth factors,
heat shock and stress. Many of these stimuli
are the same as those that also activate MAPKs
(36-39). MKP-1 is the frst-discovered MKP
and controls the MAPK signalling pathway by
inactivating these enzymes through dephos-
phorylation (40-42). MAPKs are activated by
pro-infammatory mediators and diverse stress
stimuli and therefore play a very important
role in the innate and infammatory immune
response (43). The inhibitory effect of MKP-1
on MAPK activation and therefore the modula-
tion of pro-infammatory processes indicate the
importance of MKP-1 in this cellular pathway.
Therefore the attenuation of MAPK signalling
by MKP-1 could be a promising target to re-
duce the infammatory responses mediated by
MAPK activation.
Current anti-asthma
therapies and MKP-1: what
do we know so far?
Inhaled corticosteroids are frst-line anti-in-
fammatory therapy in asthma. However, there
is increasing evidence that the combination
of an anti-infammatory corticosteroid with
long-acting bronchodilator
2
-agonists results
in superior therapeutic beneft, when compared
with each component administered alone (re-
viewed in (44)). Understanding the molecular
basis of this fundamental clinical observation
is a Holy Grail of current respiratory diseases
research as it could permit the rational exploi-
tation of this effect with the development of
new optimized corticosteroid/
2
-agonists com-
bination therapies (44). It is this question that
we have begun to address. We have focused
our investigations on the endogenous MAPK
deactivator MKP-1 as MKP-1 acts as a criti-
cal negative regulator of the myriad pro-infam-
matory pathways activated by MAPKs. We (10)
and others (45) have recently discovered that
the anti-infammatory action of corticosteroids
in ASM cells occurs via upregulation of MKP-1.
Moreover, the corticosteroid-inducible gene
MKP-1 is enhanced by long-acting
2
-agonists
(46), and the enhanced expression of MKP-1
may explain the benefcial effects of
2
-agonists/
corticosteroid combination therapies in the
repression of infammatory gene expression in
asthma (44). Thus, further investigations into
the molecular basis of MKP-1 regulation are
urgently required as this new knowledge may
lead to elucidation of optimized corticoster-
oid-sparing therapies.
How is MKP-1 regulated?
MKP-1 is a 367 amino acid protein expressed
by an immediate-early gene (37). Stimuli
which activate MAPKs also induce MKP-1
protein that then acts back on MAPKs as an
important negative feedback controller to limit
the strength and duration of MAPK-mediated
cellular signalling (reviewed in (47)). However,
the increase in MKP-1 protein levels is tran-
sient, as MKP-1 protein (expressed as a result
of increased transcription and/or mRNA stabil-
ity) then undergoes rapid degradation by the
proteasomal machinery. Investigations into
how MKP-1 is regulated will allow us to fully
explore the potential of harnessing the power
of an endogenous MAPK deactivator MKP-
1 to inhibit MAPK-mediated pro-remodelling
functions.
It is known that the activity of MKP-1 can be
regulated at different levels. There are several
approaches to regulate the expression of MKP-
1 not only on the transcriptional level but also
Asthma and Airway Remodelling
|
177
on the post-transcriptional and on the post-
translational level. Shortly after exposure to
the diverse stimuli (such as stress and growth
factors) the transcription of MKP-1 is induced
and mRNA levels are highly increased. The
mechanism by which the transcriptional induc-
tion is mediated is currently not completely
understood but since MKP-1 can be induced
by various stimuli the transcriptional induc-
tion and regulation seems to be a promising
target for the modulation of the infammatory
response (42). The post-transcriptional regula-
tion of MKP-1 stability is another mechanism
to alter the enzymatic activity of this phos-
phatase. It has been shown that the MKP-1
stability can be increased through phosphoryla-
tion by ERK1/2 and that leads to an accumula-
tion of MKP-1 in the cell and therefore may
enhance the activity of MKP-1 (42, 48). To
what extent the enhanced expression of MKP-1
has positive or maybe also negative outcomes is
not completely known. The modulation of the
interactions between MKP-1 and its substrates
is a subject of the post-translational regulation
of MKP-1 activity. The substrate specifcity de-
pends on diverse structural elements of MKP-1
and the modulation of this interaction could
also be a mechanism to enhance the phos-
phatase activity and hence the inactivation of
the MAPK pathway and therefore the effcacy of
the anti-infammatory reaction in the immune
response. If it is possible to inhibit or attenuate
the proteosomal degradation of MKP-1, that
would provide another promising opportunity
to regulate the MKP-1 activity. We are currently
working on achieving a greater understanding
of the multiple levels of regulation of MKP-1
regulation so that we can increase MKP-1 and
reduce MAPK-mediated signalling.
Our current work: how
is MKP-1 degraded?
Thus, because MKP-1 serves a crucial negative
feedback role in regulating pro-remodelling
signal transduction, discovering mechanisms to
regulate the protein level or enzymatic activity
of this endogenous MAPK-deactivator may be
exploited as a novel anti-infammatory strategy
in asthma and airway remodelling. Thus, in
order to achieve our aim of increasing MKP-1
to reduce MAPK-mediated signalling, we need
a greater understanding of the three levels of
MKP-1 regulation: (i) transcriptional; (ii) post-
transcriptional; and (iii) translational. We are
currently examining how MKP-1 is regulated
at the translational level, that is, how MKP-1 is
degraded by the proteasome the garbage bin
of the cell. As mentioned earlier, stimuli which
activate MAPKs also induce MKP-1 protein.
However, the increase in MKP-1 protein levels
is transient, as MKP-1 then undergoes rapid
degradation by the proteasomal machinery.
If we can understand how and why MKP-1
is degraded, we could design molecules that
could specifcally block MKP-1 degradation
and thus allow MKP-1 protein levels to remain
high. We are currently a long way from our
goal but our preliminary evidence obtained in
airway smooth muscle cells shows that stimula-
tion increases MKP-1 protein levels (peaking
at ~ 2 hours) but the protein degrades over
time. We have used a non-specifc proteasome
inhibitor MG132 and confrmed that we
can inhibit proteasomal degradation and keep
Time after stimulation
0 5 10 30 1 2 4 24
- MG132
(min) (h)
+ MG132
Figure C. MKP-1 is proteasomally degraded in airway smooth muscle cells.
Airway smooth muscle cells were pretreated with and without the proteasome
inhibitor MG132 (10 M), before stimulation with 10 ng/ml platelet derived
growth factor-BB. Western blotting for MKP-1 was performed.
MKP-1
MKP-1
178
|
Genes to Galaxies
MKP-1 levels high. We now need to investigate
whether we can do this just for MKP-1 protein.
Future directions and signifcance
Asthma is a widespread chronic health prob-
lem. Airway remodelling underlies asthma, but
unfortunately, the pharmacotherapy currently
available for combating remodelling has had
limited success. We need to understand how
to control airway remodelling to be able to im-
prove treatments for asthma. With our work we
will increase our knowledge of the mechanistic
basis of asthma focusing on the role of the
MAPK pro-remodelling signalling pathways.
In this chapter we have highlighted the use of
small molecule MAPK inhibitors in vitro and in
vivo and explored the potential of harnessing
the power of an endogenous MAPK deactivator
MKP-1 in inhibiting MAPK-mediated pro-
remodelling functions. It is our hope that the
elucidation of novel molecular strategies and
drug candidates targeting the pro-remodelling
MAPK signalling pathway will serve as a future
pharmacotherapeutic approach to treating and
preventing airway remodelling.
References
Elias, J. A. 2000. Airway remod- 1.
eling in asthma: Unanswered ques-
tions. Am. J. Respir. Crit. Care Med.
161(Supplement):S168-S171.
Slade, D. J., and M. Kraft. 2006. Airway 2.
remodeling from bench to bedside: current
perspectives. Clin. Chest Med. 27(1):71-85,
vi.
Mauad, T., E. H. Bel, and P. J. Sterk. 2007. 3.
Asthma therapy and airway remodeling. J.
Allergy Clin. Immunol. 120(5):997-1009.
Wiggs, B. R., R. Moreno, J. C. Hogg, C. 4.
Hilliam, and P. D. Pare. 1990. A model of
the mechanics of airway narrowing. J. Appl.
Physiol. 69(3):849-860.
Pare, P. D., B. R. Wiggs, A. James, J. C. 5.
Hogg, and C. Bosken. 1991. The compara-
tive mechanics and morphology of airways
in asthma and chronic obstructive pulmo-
nary disease. Am. J. Respir. Crit. Care Med.
143:1189-1193.
Pelaia, G., G. Cuda, A. Vatrella, L. Gallelli, 6.
M. Caraglia, M. Marra, A. Abbruzzese, M.
Caputi, R. Maselli, F. S. Costanzo, and S. A.
Marsico. 2005. Mitogen-activated protein ki-
nases and asthma. Journal of Cell Physiology
202(3):642-653.
Duan, W., and W. S. Wong. 2006. Targeting 7.
mitogen-activated protein kinases for asth-
ma. Curr Drug Targets 7(6):691-8.
Lalor, D. J., B. Truong, S. Henness, A. E. 8.
Blake, Q. Ge, A. J. Ammit, C. L. Armour,
and J. M. Hughes. 2004. Mechanisms of
serum potentiation of GM-CSF production
by human airway smooth muscle cells. Am.
J. Physiol. 287(5):L1007-1016.
Henness, S., E. van Thoor, Q. Ge, C. L. 9.
Armour, J. M. Hughes, and A. J. Ammit.
2006. IL-17A acts via p38 MAPK to in-
crease stability of TNF-alpha-induced IL-8
mRNA in human ASM. Am. J. Physiol.
290(6):L1283-L1290.
Quante, T., Y. C. Ng, E. E. Ramsay, S. 10.
Henness, J. C. Allen, J. Parmentier, Q. Ge,
and A. J. Ammit. 2008. Corticosteroids
reduce IL-6 in ASM cells via up-regulation
of MKP-1. Am. J. Respir. Cell Mol. Biol.
39(2):208-17.
Johnson, P. R. A., J. L. Black, S. Carlin, 11.
Q. Ge, and P. A. Underwood. 2000. The
production of extracellular matrix proteins
by human passively sensitized airway
smooth-muscle cells in culture: The effect
of beclomethasone. Am. J. Respir. Crit.
Care Med. 162:2145-2151.
Johnson, P. R., J. K. Burgess, Q. Ge, M. 12.
Poniris, S. Boustany, S. M. Twigg, and J.
L. Black. 2006. Connective tissue growth
factor induces extracellular matrix in asth-
matic airway smooth muscle. Am. J. Respir.
Crit. Care Med. 173(1):32-41.
Ammit, A. J., L. M. Moir, B. G. Oliver, J. M. 13.
Hughes, H. Alkhouri, Q. Ge, J. K. Burgess,
J. L. Black, and M. Roth. 2007. Effect of
IL-6 trans-signaling on the pro-remodeling
phenotype of airway smooth muscle. Am.
J. Physiol. 292(1):L199-L206.
Ammit, A. J., A. T. Hastie, L. C. Edsall, R. 14.
K. Hoffman, Y. Amrani, V. P. Krymskaya, S.
Asthma and Airway Remodelling
|
179
A. Kane, S. P. Peters, R. B. Penn, S. Spiegel,
and R. A. Panettieri, Jr. 2001. Sphingosine
1-phosphate modulates human airway
smooth muscle cell functions that promote
infammation and airway remodeling in
asthma. FASEB J. 15(7):1212-1214.
Lee, J.-H., P. R. A. Johnson, M. Roth, N. H. 15.
Hunt, and J. L. Black. 2001. ERK activation
and mitogenesis in human airway smooth
muscle cells. Am. J. Physiol. 280(5):L1019-
1029.
Burgess, J. K., J. H. Lee, Q. Ge, E. E. 16.
Ramsay, M. H. Poniris, J. Parmentier,
M. Roth, P. R. Johnson, N. H. Hunt, J.
L. Black, and A. J. Ammit. 2008. Dual
ERK and phosphatidylinositol 3-kinase
pathways control airway smooth muscle
proliferation: Differences in asthma. J. Cell.
Physiol.
Ammit, A. J., J. K. Burgess, S. J. Hirst, 17.
J. M. Hughes, M. Kaur, J. Y. Lau, and S.
Zuyderduyn. 2008. The effect of asthma
therapeutics on signalling and transcrip-
tional regulation of airway smooth muscle
function. Pulm. Pharmacol. Ther.
Ammit, A. J., and R. A. Panettieri, Jr. 2001. 18.
Invited Review: The circle of life: cell cycle
regulation in airway smooth muscle. J.
Appl. Physiol. 91(3):1431-1437.
Hirst, S. J., J. G. Martin, J. V. Bonacci, 19.
V. Chan, E. D. Fixman, Q. A. Hamid, B.
Herszberg, J. P. Lavoie, C. G. McVicker,
L. M. Moir, T. T. Nguyen, Q. Peng, D.
Ramos-Barbon, and A. G. Stewart. 2004.
Proliferative aspects of airway smooth
muscle. J. Allergy Clin. Immunol. 114(2
Suppl):S2-S17.
Oltmanns, U., R. Issa, M. B. Sukkar, M. 20.
John, and K. F. Chung. 2003. Role of c-jun
N-terminal kinase in the induced release
of GM-CSF, RANTES and IL-8 from hu-
man airway smooth muscle cells. Br. J.
Pharmacol. 139(6):1228-1234.
Peifer, C., G. Wagner, and S. Laufer. 21.
2006. New approaches to the treatment of
infammatory disorders small molecule in-
hibitors of p38 MAP kinase. Curr Top Med
Chem 6(2):113-49.
Margutti, S., and S. A. Laufer. 2007. Are 22.
MAP kinases drug targets? Yes, but diffcult
ones. ChemMedChem 2(8):1116-40.
Amrani, Y., A. J. Ammit, and R. A. 23.
Panettieri, Jr. 2001. Tumor Necrosis Factor
Receptor (TNFR) 1, but Not TNFR2,
Mediates Tumor Necrosis Factor-alpha
-Induced Interleukin-6 and RANTES in
Human Airway Smooth Muscle Cells: Role
of p38 and p42/44 Mitogen-Activated
Protein Kinases. Mol. Pharmacol.
60(4):646-655.
Hedges, J. C., C. A. Singer, and W. T. 24.
Gerthoffer. 2000. Mitogen-activated pro-
tein kinases regulate cytokine gene expres-
sion in human airway myocytes. Am. J.
Respir. Cell Mol. Biol. 23(1):86-94.
Hallsworth, M. P., L. M. Moir, D. Lai, and 25.
S. J. Hirst. 2001. Inhibitors of mitogen-
activated protein kinases differentially reg-
ulate eosinophil-activating cytokine release
from human airway smooth muscle. Am. J.
Respir. Crit. Care Med. 164(4):688-697.
Duan, W., J. H. Chan, K. McKay, J. R. 26.
Crosby, H. H. Choo, B. P. Leung, J. G.
Karras, and W. S. Wong. 2005. Inhaled
p38alpha mitogen-activated protein ki-
nase antisense oligonucleotide attenuates
asthma in mice. Am. J. Respir. Crit. Care
Med. 171(6):571-8.
Dominguez, C., D. A. Powers, and N. 27.
Tamayo. 2005. p38 MAP kinase inhibitors:
many are made, but few are chosen. Curr
Opin Drug Discov Devel 8(4):421-30.
Nath, P., S. Y. Leung, A. Williams, A. 28.
Noble, S. D. Chakravarty, G. R. Luedtke, S.
Medicherla, L. S. Higgins, A. Protter, and
K. F. Chung. 2006. Importance of p38 mi-
togen-activated protein kinase pathway in
allergic airway remodelling and bronchial
hyperresponsiveness. Eur. J. Pharmacol.
544(1-3):160-7.
180
|
Genes to Galaxies
Ammit, A. J., S. A. Kane, and R. A. 29.
Panettieri, Jr. 1999. Activation of K-p21ras
and N-p21ras, but not H-p21ras, is neces-
sary for mitogen-induced human airway
smooth-muscle proliferation. Am. J. Respir.
Cell Mol. Biol. 21(6):719-727.
Orsini, M. J., V. P. Krymskaya, A. J. 30.
Eszterhas, J. L. Benovic, R. A. Panettieri, Jr.,
and R. B. Penn. 1999. MAPK superfamily
activation in human airway smooth mus-
cle: mitogenesis requires prolonged p42/
p44 activation. Am. J. Physiol. 277(Lung
Cell. Mol. Physiol.):L479-L488.
Vlahos, R., K. S. Lee, E. Guida, D. J. 31.
Fernandes, J. W. Wilson, and A. G.
Stewart. 2003. Differential inhibition of
thrombin- and EGF-stimulated human cul-
tured airway smooth muscle proliferation
by glucocorticoids. Pulm. Pharmacol. Ther.
16(3):171-180.
Nath, P., P. Eynott, S. Y. Leung, I. M. 32.
Adcock, B. L. Bennett, and K. F. Chung.
2005. Potential role of c-Jun NH2-terminal
kinase in allergic airway infammation and
remodelling: effects of SP600125. Eur. J.
Pharmacol. 506(3):273-83.
Owens, D. M., and S. M. Keyse. 2007. 33.
Differential regulation of MAP kinase
signalling by dual-specifcity protein phos-
phatases. Oncogene 26(22):3203-13.
Jeffrey, K. L., M. Camps, C. Rommel, and 34.
C. R. Mackay. 2007. Targeting dual-spe-
cifcity phosphatases: manipulating MAP
kinase signalling and immune responses.
Nat Rev Drug Discov 6(5):391-403.
Farooq, A., and M. M. Zhou. 2004. 35.
Structure and regulation of MAPK phos-
phatases. Cell. Signal. 16(7):769-79.
Kondoh, K., and E. Nishida. 2007. 36.
Regulation of MAP kinases by MAP kinase
phosphatases. Biochimica et Biophysica
Acta (BBA) - Molecular Cell Research
1773(8):1227-1237.
Sun, H., C. H. Charles, L. F. Lau, and N. 37.
K. Tonks. 1993. MKP-1 (3CH134), an im-
mediate early gene product, is a dual spe-
cifcity phosphatase that dephosphorylates
MAP kinase in vivo. Cell 75(3):487-493.
Keyse, S. M. 2000. Protein phosphatases 38.
and the regulation of mitogen-activated
protein kinase signalling. Curr. Opin. Cell
Biol. 12(2):186-192.
Wong, H. R., K. E. Dunsmore, K. Page, and 39.
T. P. Shanley. 2005. Heat shock-mediated
regulation of MKP-1. Am J Physiol Cell
Physiol 289(5):C1152-1158.
Chen, P., J. Li, J. Barnes, G. C. Kokkonen, 40.
J. C. Lee, and Y. Liu. 2002. Restraint of
proinfammatory cytokine biosynthesis by
mitogen-activated protein kinase phos-
phatase-1 in lipopolysaccharide-stimulated
macrophages. J. Immunol. 169(11):6408-
6416.
Salojin, K. V., I. B. Owusu, K. A. 41.
Millerchip, M. Potter, K. A. Platt, and T.
Oravecz. 2006. Essential role of MAPK
phosphatase-1 in the negative control of
innate immune responses. J. Immunol.
176(3):1899-907.
Liu, Y., E. G. Shepherd, and L. D. Nelin. 42.
2007. MAPK phosphatases-regulating
the immune response. Nature Reviews
Immunology 7(3):202-212.
Abraham, S. M., T. Lawrence, A. Kleiman, 43.
P. Warden, M. Medghalchi, J. Tuckermann,
J. Saklatvala, and A. R. Clark. 2006.
Antiinfammatory effects of dexamethasone
are partly dependent on induction of dual
specifcity phosphatase 1. J. Exp. Med.
203(8):1883-9.
Giembycz, M. A., M. Kaur, R. Leigh, and 44.
R. Newton. 2007. A Holy Grail of asthma
management: toward understanding how
long-acting beta(2)-adrenoceptor agonists
enhance the clinical effcacy of inhaled cor-
ticosteroids. Br. J. Pharmacol.
Issa, R., S. Xie, N. Khorasani, M. Sukkar, 45.
I. M. Adcock, K. Y. Lee, and K. F. Chung.
2007. Corticosteroid inhibition of growth-
related oncogene protein-alpha via
mitogen-activated kinase phosphatase-1 in
airway smooth muscle cells. J. Immunol.
178(11):7366-7375.
Asthma and Airway Remodelling
|
181
Kaur, M., J. E. Chivers, M. A. Giembycz, 46.
and R. Newton. 2008. Long-acting
beta2-adrenoceptor agonists synergisti-
cally enhance glucocorticoid-dependent
transcription in human airway epithelial
and smooth muscle cells. Mol. Pharmacol.
73(1):203-14.
Wang, X., and Y. Liu. 2007. Regulation of 47.
innate immune response by MAP kinase
phosphatase-1. Cell. Signal. 19(7):1372-
82.
Brondello, J. M., J. Pouyssegur, and F. R. 48.
McKenzie. 1999. Reduced MAP kinase
phosphatase-1 degradation after p42/
p44MAPK-dependent phosphorylation.
Science 286(5449):2514-7.66
Cosmobiology:
Our Place in
the Universe
Charles H. Lineweaver
H
ere we sit on a ball of silicate
with beating hearts, opposable
thumbs and curious minds.
How did we get here? How
did the evolution of non-living things, such as
galaxies, stars and planets, create the ingredi-
ents and the conditions for the emergence of
life? Which aspects of this evolution are unique
to the Earth and which are common in the
universe? Are we alone? These cosmobiological
questions are sharpened and partially answered
by the overview presented here.
How in the universe
did we get here?
In the fctional story Hitchhikers Guide to the
Galaxy, the Improbability Drive called into
existence a sperm whale several miles above the
surface of an alien planet (Adams, 1999). As it
falls through the atmosphere:
this poor innocent creature had very little
time to come to terms with its identity as a
whale before it then had to come to terms
with not being a whale anymore Ah.!
184
|
Genes to Galaxies
Whats happening? It thought. Er, excuse me,
who am I? Hello? Why am I here? Whats my
purpose in life? What do I mean by who am
I? Calm down, get a grip nowAnd wow!
Hey! Whats this thing suddenly coming to-
ward me very fast? Very, very fast. So big and
fat and round, it needs a big wide-sounding
name likeowoundroundground!
Thats it! Thats a good name ground! I
wonder if it will be friends with me? And the
rest, after a sudden wet thud, was silence.
Like this discombobulated sperm whale, many
of us are trying to come to terms with our
identities as life forms, before not being life
forms anymore. We are hopeful that a scientifc
understanding of how we ft into the universe
can help combobulate us.
Our scientifc discombobulation begins with
the origin of the universe. Our best ideas about
Figure 2: On the largest scales we will
always be lost. This image represents
the possible multiverse. Each bubble is a
separate universe that was born from its
mother universe and which, in turn can
give birth to baby universes. Our universe
may have been born as some random
fuctuation of a patch of space-time
foam in our mother universe that went
through a process called infation. In this
diagram, our three dimensional universe
is fattened into two dimensions and is
represented by the surface of one of the
small blue bubbles. In the square box,
each black smudge represents a galaxy.
The entire box full of galaxies shows only
a small portion of our universe. The pink
circle inside the box shows the extent of
our observable universe, which is only
an infnitesimally small part of the entire
universe (i.e., of our blue bubble). We are
in the centre of our observable universe.
Figure 1 shows us the galaxies between us
and the edge of our observable universe
along one line of sight. Figure 3 is an
image of the surface of our observable
universe (the pink circle) 13.7 billion years
ago when our entire universe was flled
with a hot plasma rather than galaxies.
Unlike the fnite surface of the blue bubble
shown here, our universe may be spatially
infnite.
Reproduced with kind permission from Sky and
Telescope The Self-Reproducing Universe by
Eugene F. Mallove, Copyright @ September 1988 by
Sky Publishing Corporation.
Figure 1: How did we get here? This deep
image of a tiny fraction of the sky (~ 10
-7
)
shows ~ 10
4
of the ~10
11
galaxies in the
observable universe. The square insert is
a detail from one of the galaxies, showing
an aerobic bipedal encephalated mammal
on a moon, breathing oxygen imported
from the blue planet in the background.
We fnd ourselves on that blue planet 13.7
billion years after the Big Bang, falling
at ~400 kilometers per second through
an almost empty and possibly infnite
universe. How in the universe did we get
to be in such an unlikely situation? Images:
NASA Hubble Ultra Deep Field and NASA
68-H-1401 and AS11-40-5903.
NASA/STScI
Cosmobiology: Our Place in the Universe
|
185
the very earliest moments of the Big Bang come
from a combination of cosmology and quantum
mechanics called quantum cosmology. In quan-
tum cosmology, there is no place for unique,
one-off events rather there are ensembles
and probability distributions. Thus, quantum
cosmology suggests that the event that we
call the origin of our universe is not a unique
event. It is one of many. Quantum cosmology
suggests that our universe is just one of a pos-
sibly infnite number of other universes, which
together we call the multiverse (Figure 2). We
dont know how the universes in the multiverse
are connected to each other or whether we can
ever fnd evidence for their existence in our
universe. Some cosmologists speculate that
these disconnected universes have different
laws of physics or possibly the same laws but
with different constants, i.e. different values for
c, the speed of light or for G, the strength
of gravity. One thing seems clear though,
despite our increasing understanding of our
surroundings, our observations or our universe
and others will always be limited. Thus, on the
very largest scales we are and always will be
lost, like that sperm whale falling through the
atmosphere of an alien planet.
How did our universe begin?
The expansion and cooling of the universe is
the basis of modern cosmology and a prerequi-
site for life. In the beginning, at the Big Bang,
13.7 billion years ago, the universe was very
hot. There was no life and there were no struc-
tures in the universe. The matter, subatomic
particles, atoms and molecules that we now
take for granted did not exist. As the hot Big
Bang cooled, matter came into existence, prob-
ably about 10
-33
seconds after the Big Bang. We
arent sure how this happened, but according to
infationary models, the most dramatic events
occurred in the frst fractions of a second after
the Big Bang, during a period at the end of
infation called reheating. Vacuum potential
energy of a scalar feld became the tangible and
clumpable energy and matter that we are more
familiar with. Poorly understood symmetry
violations (Sahkarov 1967) led to an excess
of matter over anti-matter and a universe
Figure 3: The best photo ever taken of the Big Bang. The photons detected to make
this map travelled for 13.7 billion years and are the oldest photons we can detect. They
were emitted from the surface of last scattering at the edge of our observable universe
when the universe was about 380,000 years old and had a temperature of ~3000 K. As
the universe expanded, these 3000 K photons became redshifted and cooled to the 3K
photons we now observe. The pattern of hot (red) and cool (dark blue) spots has been
used to obtain the most accurate estimates of the contents, age and size of the universe.
Image: NASA/WMAP Science Team.
186
|
Genes to Galaxies
dominated by matter. Then at 10
-3
seconds
after the Big Bang, matter in the form of a
quark-gluon plasma cooled and condensed
into protons and neutrons. Within three
minutes these particles had condensed into
light nuclei during a period called Big Bang
nucleosynthesis. As the universe continued to
cool, atoms formed for the frst time about half
a million years after the Big Bang. The universe
was a thermal heat bath of photons and atoms
in chemical equilibrium. Figure 3 is a full-sky
map of the cosmic microwave background
radiation. It shows the thermal heat bath of
the universe 380,000 years after the Big Bang.
There were no stars or galaxies. Life is not pos-
sible in such an environment. In thermal and
chemical equilibrium, no free energy is avail-
able, and free energy, not just energy, is what
life requires (Lineweaver & Egan 2008).
During the 13.7 billion years since the Big
Bang, the universe expanded, the heat bath
cooled and life (at least on Earth) emerged. Life
did not emerge simply because the universe
cooled down to have the right temperature
for H
2
O to be a liquid. Life needed a source of
free energy unavailable from an environment
in chemical and thermal equilibrium. The ori-
gin of all sources of free energy can be traced
back to the initial low gravitational entropy of
the unclumped matter in the universe (e.g.,
Lineweaver & Egan 2008). The gravitational
collapse of this matter produced galaxies, stars
and planets and is the source of all dissipative
structures and activities, (including life) in the
universe. Notice in the upper right of Figure 4
the small interval of logarithmic time during
which free energy from stars has been available
to power life in the universe. The frst stars
formed about 200 million years after the Big
Figure 4: As the universe expands and cools, structures freeze out of the
undifferentiated vacuum energy and quark-gluon plasma, like snowfakes from a cooling
cloud. Structures that freeze out include, frst matter at very high energies, then protons
and neutrons, then nuclei, atoms and molecules. The thick diagonal line labeled CMB
is the temperature of the cosmic microwave background, which is the temperature of the
universe. The universe became transparent when it cooled down to about 3000 K and
atoms (mostly hydrogen) formed out of the cooling plasma of electrons and protons (see
the horizontal line labeled atoms). Figure 3 is an image of the CMB at that time. See
Lineweaver and Schwartzman (2004) for details.
Cosmobiology: Our Place in the Universe
|
187
Bang ( ~ 10
16
seconds) when hydrogen cooled
down to 50 100 K. Before this time there
were no stars and therefore no free energy to
drive life. There was also no oxygen to make
H
2
O until several million years after the frst
generation of massive stars.
Life as we know it is based on molecules;
clumps of atoms that froze out of the cooling
universe when the temperature of the universe
fell below molecular binding energies (Figure
4). Thus, the expansion and cooling of the
universe has been the most basic prerequisite
for the origin of molecules and molecular life.
But life cannot be made out of the cooling
hydrogen and helium produced in the Big
Bang. Many generations of massive stars had
to form and die before the ashes of nuclear
fusion accumulated to contain enough oxygen,
carbon, nitrogen, sulfur and phosphorus to
produce watery environments and allow the
chemical evolution of carbon molecules into
hydrocarbons, carbohydrates and life.
Four elements make up more than 99% of
the atoms in terrestrial life: hydrogen, oxygen,
carbon and nitrogen or HOCN. Add seven
more elements to this mix (S, P, Cl, Na, Mg, K
and Ca) and we have more than 99.99% of the
atoms in terrestrial life. Of all these ingredients,
only hydrogen was made in the Big Bang, the
rest were produced in the hot fusing cauldrons
of massive stars. Their ubiquity ensures that
the ingredients for life are present throughout
the cosmos.
Figure 5: Any life forms in the universe depend on sources of free energy in the
universe. These sources come in three kinds: gravitational (left), nuclear (middle) and
chemical (right). Left panel: dissipation in an accretion disk leads to angular momentum
exchange between two small masses (two light greyballs). The mass that loses angular
momentum falls in. The one that gains momentum is expelled. Accretion disks are
dissipative structures which, like more traditional life forms, must be fed must have a
source of free energy to maintain their structure. Middle panel: the binding energy
per nucleon due to the strong nuclear force provides the gradient that makes fusion
and fssion drive nuclei towards iron. Right panel: the energy that heterotrophic life (like
ourselves) extracts from organic compounds, or that chemotrophic life extracts from
inorganic compounds, can be understood as electrons sinking deeper into electrostatic
potential wells. In every redox pair, the electron starts out high in the electron donor
(light grey ball) and ends up (black ball) lower in the potential of the electron acceptor
(cf. Nealson and Conrad 1999, their Figure. 3). These three sources of free energy are not
independent of each other. For example, gravitational collapse (left) enables solar fusion
(middle) which powers life on Earth (right). Image from Lineweaver and Egan (2008).
188
|
Genes to Galaxies
There are many reasons to believe that terrestri-
al planets, broadly defned, in habitable zones
are ubiquitous in the Universe (Lineweaver
et al 2003). For example, planets are formed
in accretion disks and accretion disks are
necessary ingredients in our best models of
star formation. The latest observations and
simulations are consistent with the possibility
that rocky planets orbit the majority of stars.
Even if we accept that terrestrial planets are
common, in order for life to emerge and evolve
into something interesting, millions or even
billions of years in a clement stable aqueous
environment may be required. Supernovae are
the required suppliers of O, C, N, S and P but
if they explode nearby they can also extinguish
life. Thus, there may be a Galactic Habitable
Zone close enough to the debris of supernovae
to enjoy a complex chemistry but far enough
away from supernovae to enjoy a clement envi-
ronment for the billions(?) of years required for
the biological evolution of interesting organ-
isms (Lineweaver et al 2004).
Two ways to approach
the origin of life
Figure 6 shows the formation of the Earth and
the origin of life on Earth within the context of
the history of the universe. There are two main
ways to approach the origin of life on Earth.
One way is to start at the initial conditions of
the Big Bang at the bottom of Figure. 6 and
work your way up, forward in time, through a
series of evolutionary processes described by
cosmology, astrophysics and chemistry includ-
ing the expansion and cooling of the universe.
This is described in the previous page. This
chronological approach produces a rather
straightforward and deterministic descrip-
tion of how the universe evolved and became
conducive for life. This deterministic approach
can explain how the ingredients of life the
elements and molecular building blocks were
produced. The building blocks (or monomers)
are important for understanding the origin of
life because life seems to work on the Lego
principle. Monomers are strung together to
form polymers out of which all terrestrial life is
made: amino acids are strung together to form
proteins, nucleotides to form RNA, fatty acids
to form lipids and monosaccharides to form
carbohydrates.
However, we dont know the specifc condi-
tions of the proto-biochemistry such as the
specifc auto-catalytic molecular reactions that
allowed the correlated polymerization of these
monomers. We dont know the environments
and pathways of molecular evolution that
led to the origin of life. In the chronological
cascade from the Big Bang to the origin of life,
we are still very ignorant about the transition
from the building blocks of life to the things
we now recognize as life. Our uncertainty is
represented by the brown roots of the tree of
life shown in Figure 6. Half a dozen good ideas
are still slugging it out to explain this transition
its a work in progress.
The other way to approach the origin of life is
to start with the living organisms at the top of
Figure 6, at the ends of all the branches and
work your way down, backwards in time to the
last universal common ancestor (LUCA) of all
extant life forms. Then make some informed
guesses about the origin of life on Earth, based
on the characteristics of LUCA What did
it look like? How did it make a living? This
procedure is similar to the way linguists use
the common properties of a family of languages
to make informed guesses about the extinct
ancestor language which diverged to produce
the family. Figures 3, 4, and 5 illustrate some
of the processes of the bottom up approach,
while Figures 7 and 8 are related to the top
down approach.
From an aqueous environment on a rocky
planet, life emerged on Earth about 4 billion
years ago and branched into the three domains:
Eubacteria, Archaea and Eukarya shown at the
top of Figures. 6, 7 and 8. All life forms on this
planet that have protein factories called ribos-
omes can be classifed into one of these three
domains. These three domains are the basic
branches of the terrestrial tree of life. Figure 7
sketches the basic branches and sub-branches
of life on Earth. Most of the kinds of life that
you might be most familiar with (animals,
plants and fungi) are just three short twigs on
the tree labeled respectively Homo, Zea and
Coprinus (Figure. 7).
Cosmobiology: Our Place in the Universe
|
189
We do not know if such a tree of life exists on
other terrestrial planets. However, we can use
this tree to make better guesses about what
forms of life we should expect elsewhere. For
example, life forms at the root of this tree are
the common ancestor of all life on Earth. They
are simpler and less quirky than the life forms
they evolved into and therefore these simpler
organisms may be more representative of what
we should expect to fnd at the base of alien
trees of life, i.e., as far as predicting aliens goes,
the smart money is on hyperthermophilic bac-
teria, not vertebrates.
Consider two cosmobiological facts: (1) ter-
restrial biogenesis occurred rapidly, i.e., life
formed on Earth more than 3.5 billion years
ago, probably as soon as it could have after the
heavy bombardment subsided; (2) terrestrial
planets are not made of anything uniquelife
and planet Earth are made of the most com-
mon elements available in the Universe. These
facts suggest that life may be common on ter-
restrial planets throughout the Universe. See
Lineweaver & Davis (2002) for details.
Combining our knowledge of the cooling of the
universe, of the formation of stars and planets,
of the composition of those planets and the
earliest forms of life on Earth, is one example
of how cosmobiology brings together the study
of life forms and cosmic processes to help us
understand how we ft into the universe and
how we compare to other life forms that may
inhabit the Universe.
If we consider viruses to be alive then Figure. 7
does not show all life. If viruses or bits of RNA
played an important role in the origin of life,
then in neglecting viruses we have thrown the
baby out with the bath water. For the begin-
ning of a viral phylogeny, see Ward (2007).
The debate about what life is, and how to rec-
ognize it, is at the heart of the question: What
is our place in the universe? This is the Holy
Grail of cosmobiology. To make progress, we
need to explore the martian subsurface and
analyze the atmospheres of the nearest 100
or 1000 terrestrial planets. NASA is prepar-
ing to build the Terrestrial Planet Finder and
ESA is preparing Darwin. Both are putting
their money on using interferometric infrared
Figure 6: The history of the universe
since the big bang. The hot big bang
(bottom) produced hydrogen and helium
(labeled H and He). Clouds of H
and He gravitationally collapsed to form
stars of various masses. The massive
blue stars exploded after a few million
years and spewed into interstellar space
the ashes from the nuclei that had fused
in their cores. After ~ 9 billion years of
such reprocessing and accumulation,
our Sun formed 4.56 billion years ago
from a gravitationally collapsing cloud
of molecular hydrogen contaminated
with oxygen, carbon, nitrogen and other
heavy elements. The Earth formed from
this contamination as the accretion disk
around the young Sun fragmented from
lack of feeding.
190
|
Genes to Galaxies
Figure 7: Phylogenic tree of terrestrial life based on the 16s subunit of ribosomal RNA.
An estimate of the position of the last universal common ancestor (LUCA) of all life is at
the center of the tree, labeled Root. The deepest and shortest branches of this tree
are all hyperthermophilic: organisms that can survive above 90 C. Therefore, LUCA at
the root of the tree was probably hyperthermophilic. Life started as a hyperthermophilic
eubacteria or archaea and branched out (see Wong 2008 but also Boussau et al 2008).
Maximal growth temperatures have been used to assign colours to the branches and
thus to construct this biological thermometer on billion year time scales. The distance
from the root to the end of each branch corresponds to the same amount of time
roughly 3.5 or 4.0 billion years. Because the ticking of the 16s molecular clock is not
exactly uniform, the distances from the root to the ends of the branches are not the same
length. Among the Eucarya in the lower left are the three twigs of complex multicellular
life: Coprinus (representing fungi), Homo (humans, representing animals) and Zea (corn,
representing plants). The common ancestor of fungi, animals and plants lived ~1.5
billion years ago (Hedges et al 2004). The last 200 million years of vertebrate evolution
corresponds to the last ~2 mm of the twig labeled Homo. Diagram from Lineweaver
and Schwartzman (2004) based on Pace (1997). Near the root, pJP27 and pJP78 are
Korarcheota, the deepest and shortest branched extant organisms presumably the
extant organism that most resembles LUCA (Elkins et al 2008).
Lineweaver and Schwartzman (2004) based on Pace (1997)
Cosmobiology: Our Place in the Universe
|
191
spectroscopy to look for the traces of chemi-
cal disequilibrium as the primary biomarker
(Lovelock 1979).
Are we alone?
The answer to this important question depends
on what we means. If Are we alone? means
Are we, the life forms on Earth, part of a larger
group of life forms out there in the universe?
then we dont know the answer. We dont
know if terrestrial life is the only life in the
universebut even more problematically were
not sure what life in its most generic form is
or how we can recognize it. For more on these
doubts see Lineweaver (2006).
If Are we alone? means Are we humans the
only species of life in the universe? then the
answer is easy. No, we are not alone. There are
millions of other species of life on Earth. If we
are not alone on Earth, we cant be alone in
the universe.
If Are we alone? means Are we humans the
only species of life in the universe with human-
like intelligence? then we have a controversial
question and the topic of much debate. Many
physical scientists tend to believe that we hu-
mans are members of a larger group of func-
tionally equivalent humans and thus, we are
not alone (Sagan 1995a,b).
Many biological scientists tend to believe that
there is no evidence for such a group of func-
tionally equivalent humans and that our clos-
est relatives in the universe (chimps and other
apes) are here on Earth, not in orbit around
other stars. Thus, if, after examining our clos-
est relatives, we decide there are none with
human-like intelligence, then by our own self-
servingly narrow defnition of intelligence, we
are alone (Simpson 1964, Mayr 1995ab). This
last version of the question Are we Alone? can
be sharpened and rephrased as:
Is human-like intelligence a
convergent feature of evolution?
In other words, is there a tendency in evolu-
tion to evolve toward our kind of intelligence?
If there is, then we are likely to fnd beings
with human-like intelligence elsewhere in the
universe. If our version of intelligence is some-
thing species-specifc something that evolved
only once in the context of billions of years of
evolution on Earth we should not expect to
fnd it on other planets.
The scientists who support Sagans view, sub-
scribe to what I call the Planet of the Apes
Hypothesis that goes something like this: There
is a human-like intelligence niche. There is
selection pressure on other species (including
our ancestors) to occupy this niche. In our
absence (or on other planets) some species will
evolve into that niche and develop technology.
Carl Sagan has called the occupants of this
niche the functional equivalent of humans.
I call it the human-like intelligence niche not
the intelligence niche because generic intel-
ligence is poorly defned. Each animal species
with a brain seems to have its own version of
Figure 8: Tree of life emerging from roots
in an RNA/Viral World. Every branch is
adorned (or infected) with viruses. Viruses
may well be remnants from an earlier
epoch in which they were the dominant
life form and no stable gene lines had
yet emerged. From the viral point of view
our vertically transferred genomes are
frozen, hardly-evolving non-participants
in the lively cut and thrust of lateral gene
transfer. Image Lineweaver 2006.
192
|
Genes to Galaxies
intelligence. It is also not clear to me that a
life form must have a brain to be intelligent.
All creatures that survive and reproduce could
be said to be as intelligent as they need to
be. Bacteria, for example, have worked out
complex and simple ways of accommodating
themselves to virtually every environmental
condition that exists on the planet. Thats pretty
smart. But thats not the kind of intelligence
most people hope to fnd elsewhere in the uni-
verse. Our human-like intelligence, unlike any
other type of intelligence on Earth, has allowed
us to build radio telescopes and given us the
ability to hear and be heard across interstellar
distances. This ability that we humans have,
and that we are able to look for in others, is a
species-specifc characteristic. No other spe-
cies on Earth seems to have it.
Frank Drake is a physical scientist and a
pioneer in the search for extraterrestrial intelli-
gence (SETI). When I asked him what the best
evidence for the existence of intelligent extra-
terrestrials was, he referred me to the work of
Jerison shown in Figure 9 which seems to show
that human-like intelligence, or at least a large
brain case is a convergent feature of evolution.
In this version of the evolution of human in-
telligence, Jerison analyzes the sizes of brain
cases as a function of time and fnds a trend
toward bigger and bigger brains. He concludes
that there is some general trend in evolution
toward bigger brains. Compare this plot to my
plot in Figure 10, where I trace the evolution
of the nose size of the elephant. Looking back
through time, it is easy to see that the ances-
tors of the elephant had smaller noses than the
elephant. In fact, if I look at the evolution of
the elephant, I can fnd a defnite trend toward
bigger noses, but it would be silly to conclude
that there is a general trend in evolution toward
bigger noses.
Interpreting Figure 9 as evidence for evolu-
tionary convergence on bigger brains is as
silly as interpreting Figure 10 as evidence for
convergence on longer noses. One cannot
identify a current extreme feature in a species,
plot the trend with time of its ancestors and
then generalize that trend to other lineages.
The trend that results is specifc to your ances-
tors obligatorily so, since the recipe for such
plots is 1) identify your species most extreme
feature (a big brain, a big nose) and make that
Figure 9: The Evolution of Relative Brain Size in Groups of Vertebrates Over the Past 200
Million Years (adapted and updated from Jerison 1976, p 96, Jerison 1991, Figure. 17). This
plot purports to show an evolutionary trend towards increasing relative brain size ( = E.Q.
= Encephalization Quotient) and is probably the most well-documented evidence for
such a trend. Average living mammal E.Q. is defned as 1. The broken lines indicate gaps
in the fossil record. Variation within groups is not shown. The lineage that led to humans
is drawn thicker than the other lineages. Lineweaver (2008)
Cosmobiology: Our Place in the Universe
|
193
Figure 10: The Evolution of Relative Nose Size (= N.Q. =Nasalization Quotient, ratio of
nose length to body length) Over the Past 200 Million Years. Notice the apparent trend in
the data as, over time, N.Q. reaches its ultimate value in extant pachyderms. Notice also
that once the direct lineage that led to elephants is ignored, most of the species do not
have an increasing N.Q. This plot is meant to illustrate a point, and should not be taken
as more than a crude representation of a specious trend in N.Q. that has been largely
ignored and poorly quantifed by paleontologists. Lineweaver 2008.
the y-axis of a plot 2) plot yourself in the upper
right 3) plot your ancestors who, since you are
the extreme, will fall on a descending line into
the lower left. Thus Figures 9 and 10 are not
evidence for any general trend toward bigger
brains or noses.
In addition, heads (and therefore brains) are
monophyletic: a single species diversifed into
all extant species with heads (brains). Not only
is human-like intelligence not a convergent
feature of evolution, heads are not a conver-
gent feature of evolution. Heads were once a
species-specifc feature, thus, all heads and
brains have diverged from a single species that
had a head. Thus, heads and brains are not the
generic products of evolution but are as quirky
and unique as a single species.
Humans are unique, just like every other spe-
cies on Earth. It makes no sense to concoct
an imaginary set of which we are the only
terrestrial member and then suppose that
biological evolution elsewhere in the universe
evolves toward this set. This concoction is The
Planet of the Apes Hypothesis. It is testable.
Paleoneurology does not support it.
Carl Sagan said that our evolution represents
the universe becoming aware of itself (Figures.
12 and 13). If human-like intelligence were so
useful, we should see many independent ex-
amples of it in biology, and we could cite many
creatures that had evolved on independent
continents to inhabit the intelligence niche.
But we cant. Human-like intelligence seems
to be what its name implies species specifc.
Thus, the terrestrial record suggests that we are
as unlikely to fnd a creature with human-like
intelligence elsewhere in the universe as we are
to fnd a sulphur crested cockatoo or a naked
mole rat on another planet.
Even so, I am a strong supporter of the SETI
Institute, which uses radio telescopes to search
for extra-terrestrial intelligence. I do not expect
to fnd creatures on other planets that build ra-
dio telescopes, but I support the effort to keep
looking. Who knows what we will fnd? SETI
is the exploration of new parameter space with
new instruments a proven recipe for scientifc
discovery. However, we do not need to misin-
terpret the fossil record to justify continuing
exploration of our universe.
194
|
Genes to Galaxies
Figure 11: The Schwarzeneggerization of Life: a self-serving misinterpretation of
evolution. A muscle-bound man stands as the end product of a linear progressionthe
Great Chain of Being a ladder of life that leads to male Caucasian weight lifters. One
can create such an apparent linear trend out of the crooked phylogenetic branch of
any species. Looking back from any particular species we will fnd the evolution of the
traits of that particular species but these traits will be different from the ones listed
along the central axis here. Precisely because we can construct such a fgure from the
lineage of any species, a single example of such a construction should not be construed
as a general linear trend applicable to all life. The simple appeal of this fgure is a good
example of how easy it is to be misled into believing that the important events and
the major transitions in evolution that led to us, are important events for all organisms.
The problems with this view are detailed in Gould (1989) but are perpetuated by Smith
and Szathmary (1995). The prevalence and recurrence of this mistaken interpretation of
evolution needs to be avoided as we try to use terrestrial evolution to give us hints about
the evolution of extraterrestrial life. This Schwarzo-centric tree should be compared with
Figure. 7 which itself, because it ignores viruses, may be guilty of a similar bias against
creatures who outsourced protein production. Gatland and Dempster (1957)
Cosmobiology: Our Place in the Universe
|
195
Figure 12: Who are we? As you read this, photons are bouncing off the image and
entering your eyes. The photons are producing a pattern of excited retinol molecules.
This pattern is being sent from your retina through your optic nerves to the occipital
lobes of your bilaterally symmetric brain, where you have a molecular model of
yourself, and how you ft into the universe. Thus, patterns of molecules inside your
brain are contemplating themselves, and that, of course, is what this picture illustrates.
Understanding how the universe produced molecules and how these molecules acquired
the ability to think about themselves may be a central thread of how we are woven into
the universe. Drawing by Victor Juhasz.
Figure 13: This cartoon captures the status of a big-brained biped. Our big brains
enable us to ask important questions such as Whats it all about?, How do I ft into
the universe? On the other hand, our brains may be too big. They deceive us with self-
importance and prevent us from knowing the humble answer that every other creature
seems to know: Eat, survive, reproduce. Image Garret Hardin.
196
|
Genes to Galaxies
References
Adams, D. 1999, The Hitchhikers Guide to
the Galaxy Ballantine Books, NY
Boussau, B. et al 2008, Parallel adaptations to
high temperatures in the Archaean eon, Nature,
456, 942-946
Elkins, J.G. et al 2008, A korarchaeal genome
reveals insights into the evolution of the
Archaea, PNAS, 105, 23, 8102-8107
Gatland, K.W. and Dempster, D.D 1957, The
Inhabited Universe: an enquiry staged on the
frontiers of knowledge, McKay, NY
Gould, S.J. 1989 The iconography of an expec-
tation In W.W. Norton Wonderful Life, NY pp
22-52
Hedges, S.B. Blair, J.E., Venturi, M.L. and Shoe,
J.L. 2004 A molecular timescale of eukaryote
evolution and the rise of complex multicellular
life, BMC Evolutionary Biology, 4,2
Hinshaw, G. et al 2009. Five-Year Wilkinson
Microwave Anisotropy Probe (WMAP)
Observations: Data Processing, Sky Maps &
Basic Results, ApJSS 180, 2, 225-245, arXiv
0803.0732v2
Jerison, H.J, 1976.(see Fig. 17) -
Paleoneurology and the Evolutionof Mind.
Scientifc American 234 (1): 90-100 (plot on
page 96)
Jerison, H.J. 1991. Brain Size and the Evolution
of Mind, American Museum of Natural History,
New York.
Lineweaver, C.H. 2006 We have not detected
extraterrestrials life, or have we? In Life as we
Know it, Edt J. Seckbach, Vol 10 of a series on
Cellular Origins and Life in Extreme Habitats
and Astrobiology, Springer, Dordrecht pp 445-
457 ISBN 1-4020-4394-5
Lineweaver, C.H. 2008 Paleontological Tests:
Human-like intelligence is not a convergent
feature of evolution. In From Fossils to
Astrobiology, Eds J. Seckbach and M. Walsh,
Springer, 353-368
Lineweaver, C.H. & Davis, T.M. 2002 Does the
Rapid Appearance of Life on Earth Suggest that
Life is Common in the Universe? Astrobiology,
Vol. 2, No. 3, 293-304 , also available at http://
arxiv.org/abs/astro-ph/0205014
Lineweaver, C.H., Grether, D. & Hidas,
M. 2003 How Common are Earths? How
Common are Jupiters? Bioastronomy 2002:
Life Among the Stars edt. R.Norris, &
F.Stootman Astron. Soc. Pac. IAU Symposium
Vol 213, 41-44 astro-ph/0209383
Lineweaver, C.H. Fenner, Y. & Gibson, B. 2004
Science 303, 59-62``The Galactic Habitable
Zone and the Age Distribution of Complex Life
in the Milky Way
Lineweaver, C.H.& Schwartzman, D. 2004 ,
``Cosmic Thermobiology: Thermal constraints
on the origin and evolution of life in ``Origins:
Genesis, Evolution and Biodiversity of
Microbial Life in the Universe edt. J. Seckbach,
Vol. 6 of a series on Cellular Origin and
Life in Extreme Habitats, Kluwer Academic,
Dordrecht, also available on-line at astro-
ph/0305214.
Lineweaver, C.H.& Egan, C. 2008 Life Gravity
and the second law of thermodynamics,
Physics of Life Reviews, 5, 4, pp 225-242
Lovelock, J. Gaia: A New Look at Life on
Earth,1979, Oxford
Mayr, E. 1995a. Can SETI succeed? Not
likely. Bioastron News 7(3). Available online at:
http://www.planetary.org/html/UPDATES/seti/
Contact/debate/Mayr.htm.
Mayr, E. 1995b The SETI debate Ernst Mayr
reponds. http://www.planetary.org/html/
UPDATES/seti/Contact/debate/Mayr2.htm
Nealson, K. Conrad, P. 1999 Life: past, present
and future. Phil Trans R. Soc. Lond B 354,
1923-1939
Pace, N.R. 1997 A molecular view of microbial
diversity and the biosphere. Science 276: 734-
740.
Sagan, C. 1995a The Abundance of Life-
Bearing Planets. Bioastron News 7(4). Available
online at: http://www.planetary.org/html/
UPDATES/seti/Contact/debate/Sagan.htm.
Sagan, C. 1995b Carl Sagan responds: http://
www.planetary.org/html/UPDATES/seti/
Contact/debate/Sagan2.htm
Cosmobiology: Our Place in the Universe
|
197
Sakharov, A.D. 1967. Violation of CP invari-
ance, C asymmetry, and baryon asymmetry
of the universe. Soviet Physics Journal of
Experimental and Theoretical Physics (JETP) 5:
2427
Simpson, G.G. 1964. The Nonprevalence of
Humanoids. Science 143, 769-775
Smith J.M and Szathmary, E 1995 The Major
Transitions in Evolution W.H. Freeman, Oxford
Ward, P. Life as we Dont Know it, 2005, Viking
Wong, J.T. 2008 Root of Life, Chapter 15 of
Prebiotic Evolution and Astrobiology edt J. T.
Wong and A. Lazcano, Landes Bioscience.
The Private Life
of a Proton
Helen Johnston
V
ery few things are forever.
Molecules re-arrange and re-
make themselves constantly, in
countless chemical reactions; and
even atoms can be made and destroyed in the
interiors of stars, forging entirely new chemical
elements. Only protons are truly unchanging:
every proton in every atom in the universe has
been there since the very beginning
1
. But over
the life of the universe, those protons may have
been through many different guises. If one of
those protons could tell its story, what a story
that would be ...
Well, here is that story.
In the beginning, there was a proton.
Actually, it wasnt quite at the beginning. At the
very beginning was the Big Bang, a moment
of infnite temperature and density. The whole
of the universe we see today was compressed
into a region smaller than an atomic nucleus.
1 Actually, under some circumstances, protons can turn
into neutrons and vice-versa. However, it takes energy
to convert a proton to a neutron, so left to themselves
neutrons will decay into protons but not vice-versa.
200
|
Genes to Galaxies
Figure 1: History of the Universe. Microcosm CERN
The Private Life of a Proton
|
201
We have no laws of physics to describe what
was going on under these conditions, so our
description of the universe has to start a tiny
fraction of a second after time zero. After that
time, the universe began to expand, and as it
did so, it cooled.
The story of our proton begins just 0.01 sec-
onds after the Big Bang. Before that, the uni-
verse had been too hot and dense for protons
to exist: instead, it was a seething mass of pho-
tons
2
, electrons, positrons, neutrinos, quarks
and antiquarks. It was not until the tempera-
ture of the universe had dropped below several
million million degrees that quarks could bind
together to form protons and neutrons.
This is where we meet our proton for the
frst time.
For a while, the existence of the proton is
very transitory: every time it meets an anti-
proton the two annihilate, converting their
mass-energy into a pair of energetic photons.
These photons then spontaneously convert
the energy back into mass, producing a new
proton/anti-proton pair, which speed away
from each other.
There comes a time, however, when the
universe has cooled just enough that the
photons no longer have enough energy to
produce new particles. When that happens,
most of the particles and antiparticles annihi-
late each other one last time. Our proton was
one of the few the very few that did not
fnd an antiparticle. For each lucky particle,
30 million other particles did not make it.
One second after the Big Bang, our proton
fnds itself in a universe made up of energy
and matter, with essentially no antimatter.
For reasons we still dont understand, there was
a tiny imbalance of matter over antimatter for
every 30 million antiparticles there were 30
million and one particles. After the annihila-
tion had fnished, only this small amount of
left-over matter remained: the rest had disap-
peared into radiation. So about 1 second after
2 Electrons and positrons are examples of antiparticles,
which have the same mass but opposite electric charge.
Particle-antiparticle pairs can annihilate one another and
convert their entire energy into two photons. Matter is
made of protons, neutrons and electrons, while antimatter
is composed of antiprotons, antineutrons and positrons.
the Big Bang, there was about one proton or
neutron for every billion photons or electrons
or neutrinos.
The universe is a seething maelstrom.
Protons and neutrons smash into each other,
moving much too fast to stick together. The
entire universe still consists entirely of sub-
atomic particles.
As the temperature drops, the particles start
moving more slowly. Now when protons and
neutrons meet, they can stick together; the
strong nuclear force grabs them and binds
them together into the frst nuclei. All around
our proton, particles are sticking together
in clumps: frst two, then three and four.
The four-nucleon clump two protons and
two neutrons is the most stable: a helium
nucleus. But not fve: when a four-particle
helium nucleus is struck by another particle,
the whole lot is split apart again.
By the time the universe is a bit more than
three minutes old, nearly all the neutrons
have combined into nuclei, while most of
the protons (including ours) are still free.
About 90% of the universe is hydrogen, with
nearly all the rest made up of helium. There
is some deuterium
3
, and tiny amounts of
lithium and beryllium, but nothing else. The
frst elements have been born, albeit without
electrons: it is still too hot for the electrons
to combine with the nuclei to form atoms.
Shortly afterwards, when the temperature
becomes too low for nucleosynthesis to
take place, the production of nuclei stops.
No more elements will be formed for a
long time.
This story of how the frst elements were
formed is extremely well understood. As the
universe cooled, new particles could be made
out of old ones. We can measure the rates at
which these reactions occur in particle ac-
celerators, and by applying the concepts of
thermodynamic equilibrium, we can predict
which particles will be formed as the universe
cools. It turns out that the fnal composition
of the universe depends only on the baryon
3 Deuterium is the name given to heavy hydrogen,
hydrogen-2, whose nucleus consists of one proton and one
neutron bound together. The ordinary hydrogen nucleus,
hydrogen-1, has just a single proton.
202
|
Genes to Galaxies
This period when electrons were trapped into
atoms the recombination era
4
has one impor-
tant consequence. Once the photons were no
longer continually bouncing off electrons, they
could begin fying freely. Most have been fying
freely ever since. We can observe these photons
today as the cosmic microwave background.
Since they began travelling, the universe has
expanded by a factor of 1000, so the tempera-
ture has dropped from 3000 degrees to just 3
degrees above absolute zero.
The cosmic microwave background radiation is
almost uniform in all directions. The Wilkinson
Microwave Anisotropy Probe (WMAP) was a
satellite launched in 2001 to measure the tiny
variations in the temperature of the radiation:
the temperature over the sky ranges from
2.7251 to 2.7249 degrees Kelvin.
The universe is completely dark. There are
no stars; nothing is hot enough to produce
any visible radiation. There is no source of
light anywhere.
Once the temperature of the universe had
dropped below 3000 K, the wavelength of the
average photon making up the background
4 Actually, it should be called the combination era, since
the electrons and nuclei had never been united before.
density how many protons and neutrons there
were in a given volume of the early universe.
By measuring the abundance of elements like
deuterium in the oldest stars, we can determine
this baryon density.
It was still too hot for the electrons to com-
bine with the nuclei to form atoms, so our
proton found itself free in a sea of protons
and helium nuclei, surrounded by photons
and electrons.
The entire universe consisted of nothing but
this ionised gas: a plasma. Electrons and nuclei
moved freely about. Because electrons are very
good at scattering photons, light cannot travel
far before hitting an electron and fying off in
another direction. This has the effect of making
the universe opaque: light is scattered around
just like being inside a fog.
Nothing else much of note happens for a
long time, while the universe continues to
expand. About 380,000 years later, the tem-
perature has cooled to about 3,000 degrees.
Finally, it is cool enough for electrons to
combine with nuclei to form stable atoms
without being ripped apart again. Once it
has captured an electron, our proton is no
longer a free proton. It is now the nucleus of
a hydrogen atom.
Figure 2: The cosmic microwave background, observed by the Wilkinson Microwave
Anisotropy Probe (WMAP). The average temperature is 2.725 K; the colours represent tiny
fuctuations (0.0001 degrees) from this mean, with red regions warmer and blue regions
colder.
Image: NASA/WMAP Science Team
The Private Life of a Proton
|
203
radiation had shifted into the infrared. Nothing
in the universe was emitting visible light.
This cosmic dark age lasted for perhaps a hun-
dred million years.
Our hydrogen atom moves aimlessly as
part of the gas that makes up the universe;
almost, but not quite, completely uniform. By
random chance, in some regions the atoms
are slightly closer together than in other
regions. This means they have slightly more
mass, so their gravity pulls in more material,
so they get denser still. By such means, little
by little, the universe gets lumpier.
In the dark, things were happening. The mat-
ter was distributed almost but not quite evenly
through the universe: we still see the imprint
of these tiny fuctuations in the background
radiation. As time went on, the clumps of mat-
ter grew; gravity was assembling the compo-
nents of the universe. The physics of how this
happened is extremely complicated: we need
supercomputer simulations to understand how
structures grew. These simulations show that
the matter develops into a web of flaments,
with voids separating the denser regions. We
see these flaments today in maps of galax-
ies. The 2dF Galaxy Redshift Survey, which
was done at the Anglo-Australian Telescope,
measured the distances to nearly a quarter of a
million galaxies, enabling astronomers to make
a three-dimensional map of the universe. The
distribution shows clusters and flaments, sepa-
rated by vast voids almost devoid of galaxies.
For a long time, our hydrogen atom drifts.
For millions of years the drift is barely per-
ceptible, but gradually it becomes apparent
that the gas is getting denser, and that it
is drifting in a particular direction. The gas
cloud containing our hydrogen atom is now
stretched out like a long thread. Then at last,
something has changed. Millions of light
years away in the direction the cloud is drift-
ing, there is light: the frst light that has been
Figure 3: Snapshots of a very large
volume of space in the Millennium
Simulation, which followed the formation
of galaxies and clusters. The yellow points
represent individual galaxies.
Images: G.Lemson and the Virgo Consortium
204
|
Genes to Galaxies
Figure 4: A slice of the universe from the 2dF Galaxy Redshift Survey: each dot is
a galaxy. Matthew Colless
at higher redshift have all their blue light ab-
sorbed by neutral hydrogen gas, while quasars
at lower redshift do not. Re-ionisation almost
certainly did not happen all at once; instead,
bubbles of ionised gas formed around stars (or
quasars). As the number of bright objects grew,
the bubbles merged together and cleared up
the fog of neutral hydrogen, allowing the blue
light to travel freely.
Evidence is beginning to suggest that it was
stars that frst re-ionised the universe. The most
distant quasars yet observed already show the
presence of elements heavier than hydrogen
and helium, which means (as we shall see) that
there must have already been massive stars be-
fore these quasars were born.
Composed only of hydrogen and helium (and a
tiny amount of lithium), these frst stars would
have been very different from the stars forming
today. Theory predicts they would not only
have been much hotter than stars forming now,
but also that they could have been much more
massive. Stars forming today cannot be more
massive than about 150 times the mass of our
Sun. Beyond that mass, the star produces so
much radiation that the outward pressure of
seen since the universe cooled below 3,000
degrees. Far ahead, one of the frst stars in
the universe is shining.
Eventually, the frst objects which produced
light were born. This light not only illuminated
the darkness, but also stripped the electrons off
the atoms in the interstellar gas again. We are
still not sure which objects were responsible
for this cosmic re-ionisation. They had to be
objects producing large numbers of energetic
photons: hydrogen is ionised by radiation with
wavelengths shorter than 91.2 nm, which are
ultraviolet photons. The most likely candidates
are either quasars or the frst stars. Quasars
are supermassive black holes, which are ac-
creting gas from a swirling disk and sending
narrow jets of high-speed particles and radia-
tion towards us. We know the universe was
already re-ionised by the time the universe was
1 Gy old
5
, at a redshift of 6, because quasars
5 Redshift describes how much the wavelength of the light
which reaches us has been stretched by the expansion of
the universe since it left the source. More distant objects
have higher redshifts, and so when we observe an object at
high redshift, the light has been travelling since a long time
in the past. The relation between redshift and age of the
universe is given in Table 1, see end of chapter.
The Private Life of a Proton
|
205
Figure 5: Cosmic reionisation in the history of the Universe. S. G. Djorgovski et al., Caltech.
Produced with the help of the Caltech Digital Media Center.
206
|
Genes to Galaxies
the radiation exceeds the inward pull of grav-
ity, and the star tears itself to pieces. The very
frst stars, however, could potentially grow to
be much more massive: several hundred, per-
haps even up to a thousand solar masses. Such
stars would have extremely short lifetimes a
million years or less after which they would
explode, seeding the interstellar medium with
heavy elements. Their collapsing cores may
even have provided the seeds which grow into
the massive black holes we see at the centres of
quasars and galaxies.
The region towards which our hydrogen
atom is falling is now perceptibly a proto-
galaxy. At its centre is a black hole, formed
from the embers of one of the dying frst
stars. Since its formation it has grown con-
siderably, by merging with other black holes,
and by sucking down enormous quantities of
gas. Surrounding it is a cloud of stars formed
from the gas that continues to accumulate.
The gas cloud containing our proton gradu-
ally swirls towards the centre of the growing
galaxy. As smaller clumps come too close
and are pulled in, some of the gas is fung
completely away, doomed to swirl forever
in the almost empty regions of intergalactic
space. Other gas fnds itself being hurled
towards the centre of the galaxy. There it is
pulled into a swirling, super-heated accretion
disk around the black hole, where it will even-
tually disappear into the event horizon and
be lost forever, or else squirted at nearly the
speed of light right out of the galaxy in twin
jets. Our proton avoids both of these fates;
instead, it fnds itself near the centre of a
dense cloud, which gets denser as more gas
collides with it and compresses it.
Whether they were formed in the frst stars,
or collapsed directly from the gas, or grew
from seeds of primordial black holes created
Figure 6: The radio galaxy Centaurus A, showing twin jets of matter being ejected from
the central black hole. These jets can be seen at X-ray and radio wavelengths.
NASA/CXC/SAO
The Private Life of a Proton
|
207
in the frst instants of the Big Bang, we know
that massive black holes already existed and
were growing less than a billion years after the
Big Bang. The most distant quasar currently
known has a redshift of 6.43, so it was formed
when the universe was only 0.87 Gy old. Radio
galaxies are also powered by supermassive
black holes, but the jet is seen side-on, so we
see radio emission from the jets. Radio galaxies
are known at redshifts of up to 5.19, when the
universe was just over 1 Gy old. So the black
holes must have been formed very early on
in the universe. Did they exist frst and then
galaxies grew around them? Or did the galaxy
and the black hole both form together? We still
dont know. We do know, however, that almost
every galaxy has a massive black hole at its
heart, and that the bigger the galaxy, the bigger
the black hole. This suggests that the growth
of the galaxy and the black hole are somehow
intimately linked.
However they began, the evidence suggests that
both the galaxy and the black hole at its heart
grow as a result of the merging of galaxies.
Everywhere we look, we see signs of galaxies in
the process of colliding, or showing evidence of
collisions in the not-too-distant past. And the
further back we look, the more common these
collisions seem to be. When galaxies collide,
the stars almost never collide: their physical
size is so small compared to the vast distances
between them that they just pass freely past
each other. However, the enormous gas and
dust clouds in both galaxies do collide: the
gas is compressed, which triggers more star
formation. Meanwhile, some of the gas and
stars are fung out in huge tidal tails, while
some is sent spiralling towards the centre of
the galaxy, where it can feed the black hole.
Figure 7: A series of interacting galaxies observed by the Hubble Space Telescope.
ESA/Hubble
208
|
Genes to Galaxies
Our own Milky Way galaxy contains the debris
of many dwarf galaxies it has swallowed up in
the past, and it is currently in the process of
devouring a few more; the Magellanic Clouds
will be devoured within the next few hundred
million years.
Over millions of years the gas cloud gets
denser and colder, and our proton (now a
hydrogen atom) fnds itself in a molecule for
the frst time: two hydrogen atoms are bound
together as molecular hydrogen, H
2
.
The interstellar gas is the raw material from
which stars form. A cloud of gas has a tendency
to collapse under its own gravity, but this in-
ward pressure is resisted by the gas pressure.
This is suffcient to resist the collapse until a
critical threshold is passed, when the collapse
becomes unstoppable. This threshold mass
depends on the temperature and density of
the cloud, with colder and denser clouds more
likely to collapse. So stars tend to form in the
coldest, densest regions of gas; these regions
are called giant molecular clouds.
A typical giant molecular cloud might be
50100 light years across and contain a million
or more solar masses of material. The gas is
now not just the pristine material made in the
frst few minutes after the Big Bang; the frst
stars polluted the interstellar gas with heavy
elements when they exploded. So by the time
this second generation of stars begins to form,
the gas cloud already contains small amounts
of (amongst other things) carbon, nitrogen,
oxygen, and other elements. Astronomers can
measure the proportion of heavy elements in
the spectra of stars, and fnd that older stars
have signifcantly lower proportions than
younger stars. In our own galaxy, these low-
metallicity stars
6
are found primarily in the
Galactic bulge and in globular clusters, while
younger, more metal-rich stars like our Sun are
found in the disk of the galaxy.
When the giant molecular cloud starts to col-
lapse, it continues under its own momentum.
More and more gas falls inwards as the collapse
accelerates. Multiple clumps develop in the
cloud, as denser-than-average regions pull in
more and more gas. Eventually the cloud frag-
ments into hundreds of small dense globules,
each of which will eventually become a star.
The collapse is fastest near the centre of each
globule where, inside a cocoon of gas and dust,
the dense core of gas is getting hotter as the ki-
netic energy of the accreting matter is convert-
ed into heat. As the density increases the cloud
becomes opaque, trapping the heat within the
cloud. This then causes both the temperature
and pressure to rise even more rapidly the
collapsing cloud is now a protostar.
The cloud containing our proton has been
accumulating mass, getting denser and
more massive as more gas falls in. Once
the runaway collapse has started, the gas
containing our proton begins its long fall
towards the dense knot that will become the
newborn star. The gas heats up as it falls; frst
6 To an astronomer, every element other than hydrogen
and helium is called a metal, so oxygen and carbon are
described as metals. Only the frst generation of stars,
made from the primordial gas of hydrogen and helium, was
metal-free.
Figure 8: The young star cluster NGC 602
in the Small Magellanic Cloud, showing
hot young stars just emerged from their
birth cloud.
NASA, ESA, and the Hubble Heritage Team
The Private Life of a Proton
|
209
the molecules are stripped apart, then the
electrons are ripped from the atoms. When
the collapse fnally ends, our proton fnds
itself near the centre of a young, massive star,
about 25 times the mass of our Sun.
The collapse only comes to an end when the
star fnds a source of energy to balance the
inexorable inward pull of gravity. That source
is nuclear fusion: when the temperature at
the core reaches about 15 million degrees,
hydrogen nuclei can begin to fuse together to
form helium, just as they did in the frst few
minutes after the Big Bang. Energy is a product
of that fusion, so as each set of four hydrogen
nuclei fuses into helium via a series of nuclear
reactions, energy is produced which increases
the temperature and pressure of the stars core
enough that it can resist the inward pull of
gravity. A star has been born.
Our proton sits near the core but not in it.
Here, where our proton sits, a bit less than
a quarter of the way out from the core, the
temperature is lower. Unprotected by their
electron shells, protons regularly collide, but
their positive charge means they just bounce
off each other. It is only deep in the core,
more compressed by the great weight of the
star, that the nuclei are moving fast enough
to collide and form new elements: frst deu-
terium, then helium.
This conversion produces enough heat to
support the immense mass of the star against
the inexorable pull of gravity.
As long as the star can continue fusing hydro-
gen to helium in its core, it can maintain its
equilibrium against the pull of gravity. The star
stays like this for 6.6 million years, steadily
converting the hydrogen in its core to helium:
the star is a main sequence star. Outside the
core, where our proton sits, no fusion is taking
place: the material of the star is still the same as
the original gas cloud from which it was born:
mostly hydrogen, with some helium and some
trace amounts of other elements left over from
previous generations of stars.
For six and half million years, nothing much
has changed for our proton. Enormous
quantities of radiation food past every
second, produced in the core and fowing
through the star to its surface, there to shine
into space.
But this situation cannot last. Eventually the
time comes when the hydrogen in the core is
exhausted. When that happens, the core can no
longer support itself against gravity, so it starts
to collapse. When it does so, it heats up, and
hydrogen just outside the core fnds itself hot
enough to fuse into helium for the frst time.
This sudden increase in energy forces the outer
layers of the star to swell up dramatically: the
diameter of the star increases by a factor of
200. The outer layers, being so much larger,
also cool dramatically, so the star becomes
enormously large and red: a red giant star. If
this star replaced our Sun, it would stretch past
the orbit of Jupiter.
Meanwhile, the helium core is still collaps-
ing and heating up. Eventually, it becomes
hot enough for helium to fuse: this takes
much higher temperatures, about 100 million
degrees. But eventually the helium is also ex-
hausted: then the collapse re-commences. The
cycle repeats: each time a fuel is exhausted, the
core begins to collapse once more, which heats
it up even higher, so that even heavier elements
can fuse, which produces more energy to sup-
port the star. The fusion of these nuclear fuels
goes faster and faster as the atomic number
increases, both because there are fewer atoms
to fuse, and less energy is released each time.
At last something changes. The pressure
beneath our proton drops, and it starts to
fall inwards. The fall is stopped as the gas
beneath is more compressed, but now the
temperature is higher. Several times this
collapse and halting happens, with the tem-
perature increasing each time. At last the day
comes when, instead of bouncing off other
protons, the particles collide and stick: our
proton is now part of a deuterium nucleus.
Almost immediately, this fuses with two more
particles to form frst helium-3 and then he-
lium-4. Later, after more collapse of the core,
this helium-4 nucleus fuses with two others to
form a carbon-12 nucleus.
Once silicon has fused to iron, however, there
is no next step. Iron is the most stable nucleus,
and does not release energy when it is fused:
adding anything else to the nucleus costs
210
|
Genes to Galaxies
energy instead of producing it. The star has
reached the end of the line, and can no longer
support itself. Gravity has won.
The core of the star collapses inwards. The
inwards pressure forces electrons and protons
in the core to combine to form neutrons. These
neutrons are squeezed so tightly together that
in less than a second the whole core of the star,
weighing about one and a half times the mass
of our Sun, is compressed to a sphere only 15
km in diameter: it has become a neutron star.
Meanwhile, the outer layers of the star are still
falling, oblivious to what is happening to the
core. When these layers meet the newborn
neutron star, they bounce off it so hard that
they are ejected outwards again at a substantial
fraction of the speed of light. This creates a
shock wave which blasts the whole envelope of
the star outwards at tremendous speed. When
this blast wave reaches the surface of the star,
it becomes visible as an enormously expanding
freball: a supernova.
Sitting in the layer of carbon, our proton (in
its carbon nucleus) has no warning of the cat-
astrophic events that have taken place deep
below it in the core of the star. The frst sign
that something has changed is that the pres-
sure beneath the layer suddenly drops; the
star begins to collapse. With nothing sup-
porting it from beneath, the outer layers of
the star, including the carbon atom contain-
ing our proton, begin to fall inwards. Seconds
later, however, the blast wave exploding
outwards through the star roars past, and the
gas is exploded outwards. All around, nuclei
are being fused with other nuclei to form
heavier elements, and bombarded by a food
Figure 9: Chandra X-ray image of the supernova remnant Cassiopeia A.
NASA/CXC/SAO
The Private Life of a Proton
|
211
of neutrons in the wake of the blast. Within
seconds, elements up to uranium are formed,
in the crucible of a supernova explosion.
Our carbon nucleus is swept outwards as part
of an expanding shell of gas. As it expands,
the shell cools, and after about a hundred
thousand years stops glowing. The remnant
of the star, now light years behind, is visible
for a few million years as a pulsar, then it too
fades. The gas from the explosion, no longer
discernible as a shell, mingles with the inter-
stellar medium.
Without supernova explosions, there would
be no heavy elements from which to form
(amongst other things) rocky planets. Recall
hydrogen, helium and a tiny bit of lithium
were the only elements formed in the Big Bang,
and until the frst stars formed nearly a bil-
lion years later, they were the only elements
in the universe. Once the frst stars had been
born, heavier elements like carbon and oxygen
were created in their cores, but these elements
were locked up, inaccessible beneath layers of
unburnt hydrogen. Supernova explosions not
only liberate these elements into interstellar
space, but are also responsible for creating all
the elements heavier than iron in the explosion
itself
7
. All the stars in our Galactic neighbour-
hood, including the Sun, have about 1% of
their mass composed of elements heavier than
helium. All these elements must have come
from earlier generations of massive stars which
lived their lives, then exploded as supernovae,
seeding the surrounding gas with the new ele-
ments. This gas, now enriched with heavy ele-
ments, can then be incorporated into new stars.
Eventually, our carbon atom fnds itself in
another cloud of cold, dense gas. A nearby
supernova triggers the collapse of this cloud.
Again, the gas is drawn inwards to where
the densest regions are pulling in ever more
material, eventually to reach high enough
temperatures that nuclear fusion begins and
stars are born.
7 There is a tiny number of elements that are formed
in different ways, like beryllium, formed when cosmic
rays split heavier nuclei in the interstellar medium, or
molybdenum, formed in the atmospheres of red giant
stars. Every other element in the periodic table is made
inside stars.
Figure 10: Protoplanetary disks around
stars in the Orion Nebula, from HST.
NASA, ESA, and the Hubble Heritage Team
212
|
Genes to Galaxies
This time, our carbon atom is not in the
dense centre of the cloud, so by the time the
new star begins to shine, it is trapped in an
icy body at the outer edges of a giant disk
swirling around the star.
As the centre of the cloud collapses, the outer
regions fatten into a disk surrounding the pro-
tostar. The Hubble Space Telescope has taken
pictures of these disks in regions like the Orion
Nebula, showing that they are common around
young stars. It is from a disk like these that the
Solar System formed.
In the inner regions of the disk, dust and
particles condense out, then stick together,
bumping and colliding and growing in size
until the fragments, now called planetesimals,
have grown to about 1 km in size. Now their
gravity starts assisting with their growth: the
larger they grow, the more matter they attract.
The largest planetesimals sweep up all the mat-
ter within their reach, until we are left with a
hundred or so proto-planets, each the size of
our Moon or larger, orbiting the infant Sun.
Over the next hundred million years or so, this
number was reduced to the current handful of
planets as the proto-planets cross orbits and
collide in giant impacts. Every old surface in
the Solar System bears witness to having been
battered by impacts of all sizes.
Orbiting beyond the outermost planets were
the left-over planetesimals, which never coa-
lesced into a planet. We still see this disk of
left-over bodies as the Kuiper Belt, a region
beyond the orbit of Neptune containing prob-
ably 70,000 or more small icy bodies more
than 100 km in diameter. Pluto and the newly-
discovered dwarf-planets like Haumea and
Makemake are just the largest members of the
Kuiper Belt.
Six hundred million years after the planets
formed, something is happening in the end-
less cold at the edge of the Solar System.
As they orbit, the icy bodies feel new and
Figure 11: Every old surface in the Solar
System bears witness to having been
battered by impacts of all sizes. From top
to bottom: Callisto, Mercury and Mimas.
The Private Life of a Proton
|
213
different pulls; orbits that were previously sta-
ble are perturbed. Chaos ensues; some bod-
ies are fung outwards, but many others are
hurled inwards, towards the inner solar sys-
tem. The icy rock containing our carbon atom
is one of them. It hurtles towards a small
rocky world circled by one large moon...
Simulations of the formation of the planets
suggest that Uranus and Neptune probably
formed much closer to the Sun than they are
now. The four largest planets interacted with
each other and with the disk of icy planetesi-
mals which circled beyond them. The orbits
slowly expanded, until after about 700 million
years, the orbit of Saturn came into 2:1 reso-
nance with Jupiter, which means that Jupiter
orbited the Sun exactly twice for every one
of Saturns orbit.
This made the orbits of Uranus and Neptune
unstable, and their orbits expanded outwards
into the disk. Planetesimals were scattered in
all directions; some were fung outwards, and
some were sent careening into the inner Solar
System. This late heavy bombardment left scars
on most planets and satellites in the solar sys-
tem. It produced the great basins of the maria
on the Moon, and may have contributed to the
atmospheres of the inner planets. None of the
rocks brought back from the Moon were older
than 3.9 billion years, which is 600 million
years younger than the age of the Solar System.
Any atmospheres the terrestrial planets had
at the beginning would have been lost during
the worst of the heavy bombardment. As the
rate of impacts began to ease, however, the
planets began to cool. Gases trapped in the hot
rocks were gradually released, and combined
with the volatiles (water, carbon dioxide etc.)
brought by comets and asteroids from the
outer solar system to gradually build up an
atmosphere. On Earth, once the temperature
dropped below 100 C, water vapour could
condense out and the oceans begin to form.
Figure 12: The near side of the Moon,
taken by the Galileo spacecraft on its way
to Jupiter. The dark areas are the maria:
impact basins flled with lava from ancient
volcanic eruptions.
Only inside stars can transmutation of ele-
ments take place, because only inside stars do
we fnd the enormous temperatures required.
Outside a star, a proton in the nucleus of an
atom is almost certain to stay there forever.
However, atoms can form an enormous variety
of molecules with other atoms, and molecular
bonds can form and break at much lower tem-
peratures. Carbon in particular forms bonds
with many elements, and can form molecules
of great complexity.
We dont know how long it was after the late
heavy bombardment before conditions were
right for life to form, but the evidence sug-
gests it wasnt long. The earliest evidence for
life comes from the study of isotope ratios
of carbon-12 to carbon-13 in rocks from 3.8
billion years ago, suggesting that life arose a
mere 100 million years after the late heavy
bombardment stopped.
The cataclysm of the impact that delivered
our carbon atom to the Earth has subsided;
the vaporised material from the icy planetesi-
mal has mixed with the existing atmosphere.
Sometime later, our carbon atom joins with
two oxygen atoms to form carbon dioxide,
the principal component of the atmosphere
of the young Earth. Soon it fnds itself dis-
solved in the newly-formed oceans. The en-
ergetic UV radiation encourages many differ-
ent compounds to form and re-form, so our
carbon atom goes through a continual cycle
214
|
Genes to Galaxies
Here are some suggestions for popular-level books covering some of these ideas.
The First Three Minutes: A Modern View Of The Origin Of The Universe by Steven Weinberg
(Basic Books, 1993)
Big Bang by Simon Singh (Fourth Estate, 2004)
The Birth of Stars and Planets by John Bally and Bo Reipurth (Cambridge UP, 2006)
Cosmic Catastrophes: Exploding Stars, Black Holes, and Mapping the Universe by J. Craig
Wheeler (Cambridge UP, 2007).
The Story of the Solar System by Mark A. Garlick (Cambridge UP, 2002)
Table 1: Redshift and lookback time
Redshift Fraction of current age
Time since Big Bang
(in Gy = 10
9
years)
1100 0.0028% 380,000 y CMB
20 1.3% 0.2 Gy
Reionisation
10 3.5% 0.5
5 8.8% 1.2
Peak of galaxy
formation
2 24% 3.3
1 57% 5.9
0.5 63% 8.6
0.2 82% 11.3
0 100% 13.7 Now
of new confgurations: methane, ammonia,
simple amino acids.
One day, a completely new type of molecule
emerges, built around our carbon atom. This
molecule and its descendants will eventu-
ally transform the planet itself, changing
its atmosphere, its surface, its oceans. It is
a molecule that can reproduce itself. Our
proton has made the next step in its long
voyage, from galaxies to genes...
Further reading:
The Private Life of a Proton
|
215
Research at
the School
of Physics
T
his chapter will give some high-
lights of the history of the School
of Physics at the University of
Sydney and a more detailed
description of current activities, including the
felds of research undertaken here. It will also
give brief snapshots of arguably our most pres-
tigious scientists, the fve Australian Research
Council (ARC) Federation Fellows who are at
present working in the School. Some words on
what the future might hold for the School com-
pletes the chapter.
Some Historical Highlights
The School of Physics occupies a beautiful
heritage building, which was built in 1924
from a design of the acclaimed architect
Lesley Wilkinson on the main campus of The
University of Sydney.
The present outstanding reputation of the
School, in Australia and internationally, had its
genesis in the appointment of Professor Harry
Messel as Head of the School in 1952. His
early achievement was to appoint a number of
218
|
Genes to Galaxies
bright young professors who were to emerge as
leaders in their felds. For example, the noted
theorist Professor Stuart Butler and Professor
Hanbury Brown who built an optical interfer-
ometer at Narrabri, in regional NSW, which lat-
er provided the impetus for the present Sydney
University Stellar Interferometer (SUSI). By
1960, Professor Bernard Mills also joined the
Department. He designed and built the radio
telescope at the Molonglo Observatory near
Canberra. Another star who was an alumnus
of the School, and later an academic, is Lord
Robert May, who was President of the Royal
Society.
A vibrant research environment was generated
by Professor Messel and continues today. He
appointed such leading scholars as Professor
Donald Melrose, a world-ranked theoretical
astrophysicist. Professor Melrose is currently
our only Fellow of the Australian Academy
of Sciences. The Academy elects Fellows
on the basis of their exceptional contribu-
tions to science, which are nationally and inter-
nationally recognised.
The Present School in 2009
The legacy of Professor Messel is refected in
the number of outstanding researchers and
teachers who are enthusiastic about work-
ing here. Over the past decade the School of
Physics has been spectacularly successful in
research, with national competitive grant in-
come more than doubling and the number of
research staff increasing from 20 to 80.
The School is also noted for its excellence
in teaching with several members of staff,
Professors Geraint Lewis and Tim Bedding,
Associate Professor Manjula Sharma, Drs John
OByrne and Joe Khachan all winning teaching
excellence awards in recent years. The number
of postgraduate research students has doubled
in this period and is continuing to rise. In
particular we have been successful in attracting
Honours students to work in our active and
diverse research groups, with the number (40)
increasing three-fold since 2000.
The research in the School covers all the basic
themes in experimental, observational, compu-
tational and theoretical physics. The particular
felds include astronomy and astrophysics,
medical physics, space physics, materials sci-
ence and plasma physics (both laboratory
and astrophysical), photonics and optics,
quantum science, particle and nuclear phys-
ics, computational biophysics and condensed
matter physics.
The astronomers and astrophysicists study a
wide range of research topics including cosmol-
ogy and the early Universe; the vexed questions
of dark matter, dark energy and the origin of
cosmic magnetism; using the Universitys and
other world-class telescopes to investigate
asteroseismology, galactic archaeology, stellar
and galaxy formation and evolution. A related
area of research is space and solar physics,
where solar fares, the Suns magnetic feld and
complex plasmas are modelled. Simulations of
plasma instabilities and self-organising systems
are part of a wider research effort in complex
systems, which also encompasses modelling the
dynamic functionality of the brain.
Research at the School of Physics
|
219
Biomedical physics is an increasingly im-
portant area of research in the School, with
academic staff investigating the interaction
and effects of radiation with matter to apply
to radiation oncology and diagnostic imaging
as well as modelling ion transport across cell
membranes. Surface modifcation to produce
bioactive sensors are carried out by the applied
physics group. Among other experimental
developments they are pioneering the prepara-
tion of novel nanolaminate materials for high
temperature operations in industry, using
plasma deposition.
The School has strengths in many areas of
theoretical physics, including single atom
modelling to understand the properties of mat-
ter and surfaces, and working with quantum
entanglement to advance quantum information
theory. This work ties well with effort in ultra-
high precision measurements using photons
and a new area of experimental physics re-
search called mesoscopic physics, which looks
at the quantum properties and behaviour of
atoms and single electrons using macroscopic
techniques.
One area of research that has developed a
strong international reputation is in optics
and photonics. Fundamental science is be-
ing carried out to develop a photonic chip,
to enable terabit data rates and to understand
non-linear optical signal processing. Since
2003, the School has been headquarters for
the ARC Centre of Research Excellence for
Ultrahigh-bandwidth Devices for Optical
Systems (CUDOS), led by Professor Benjamin
Eggleton. CUDOS is one of only two Centres
of Excellence headquartered at the University
of Sydney. These centres have nodes in sev-
eral institutions around the country, either
Universities or research institutions. To crys-
tallise Sydneys leadership in photonics, we
recently launched the Sydney Institute for
Photonics and Optical Science (IPOS), which
will be the focus for expanding our high
profle in this area. Strong links exist with the
new research feld of astrophotonics, bridging
astronomy and photonics, where innovative
techniques are used to build optic-fbre based
instruments for world-class telescopes.
We are also part of the worldwide collabora-
tions researching fundamental particle physics
with the Large Hadron Collider at CERN, near
Geneva in Switzerland. As well as high-energy
particle physics, there is a group investigating
accelerator-driven sub-critical nuclear reactors
as a safer option for nuclear power generation.
To add to our diversity, we accommodate a
group working on the quantitative analysis of
humanitys impact on our environment, and
one with a focus on physics education and the
question how should we best teach physics?
Many of the research groups are led by ARC
Federation Fellows, which is the most prestig-
ious research fellowship offered in Australia.
In 2008 there were 6 in the School, the largest
number in any research area in the country and
more than the total awarded to several entire
220
|
Genes to Galaxies
Universities. Currently we have 5 Fellows
and a brief description of their research is
given below.
As well as the Federation Fellows the School
hosts another 25 researchers who have been
awarded nationally competitive Fellowships,
including 5 ARC Professorial Fellows and 5
ARC Queen Elizabeth II Fellows. The intel-
lectual fre-power in the School is impressive.
One measure of excellence is that we published
over 450 refereed publications in 2008 alone,
including papers in the highest impact journals
such as Science, Nature Photonics and Physical
Review Letters.
A large refurbishment has recently been un-
dertaken to improve the experimental physics
facilities in the School and to accommodate 15
staff and students who have transferred from
the Universitys Optic Fibre Technology Centre.
They are now members of the School and part
of IPOS. The new laboratories also provide
facilities to begin research in mesoscopic phys-
ics and nanotechnology. As well as internal
collaborations between many of the research
groups, the academic staff have multiple links
with top international research groups. These
networks are essential for maintianing our
excellent research output. A brief snapshot of
the research of our Federation Fellows will give
some insight to the exciting and challenging
science questions they are tackling.
Our ARC Federation Fellows
Professor Marcela Bilek
The research focus of Professor Marcela Bilek is
the synthesis of new materials and surfaces us-
ing plasma processes. In recent years, she and
her team have developed plasma deposition
systems capable of delivering sub-monolayer
quantities of constituent elements in a highly
ionised form. The ions are guided by magnetic
felds to the growth surface where the material
is forming. The energy with which they arrive
is controlled by electric felds. Professor Bilek
has demonstrated that fne control over the
composition and microstructure of the growing
materials can be achieved by tuning the con-
stituent fuxes and their ion impact energies.
The structure and properties of the new ma-
terials are studied by advanced microanalysis
methods such as infra-red spectroscopy, X-ray
photoelectron spectroscopy, secondary neu-
tral mass spectroscopy, transmission electron
microscopy (TEM), X-ray diffraction, spectro-
scopic ellipsometry etc. Our understanding of
the structure and properties is extended by ab-
initio molecular dynamics simulations, using
codes to implement density functional theory
methods. Materials of particular interest for
applications include versatile bioactive protein
immobilisation surfaces for use in biosensors,
medical diagnostic and implantable devices
and transparent conducting oxides for use as
transparent electrodes. She is also studying a
new class of materials called MAX phases for
applications in extreme temperature environ-
ments. These materials combine the properties
of ceramics and metals.
Professor Joss Bland-Hawthorn
Professor Joss Bland-Hawthorn is a world
leader in the study of galaxy evolution. In
collaboration with Professor Ken Freeman,
he developed the feld of galactic archaeology
and the technique of chemical tagging, which
uses the detailed chemical and kinematic
Four of the ARC Federation Fellows in
the School of Physics in 2008: Professor
Ben Eggleton, Professor Marcela Bilek,
Professor Cathy Stampf, Professor
Bryan Gaensler.
Research at the School of Physics
|
221
information of millions of stars to reconstruct
the sequence of events leading to the formation
of the Galaxy. His research inspired massive
stellar surveys, such as the Radial Velocity
Experiment (RAVE) to measure the positions
and proper motions of 50 million stars and the
HERMES project to measure the phases-space
orbits and chemical abundances of stellar as-
sociations in our Galaxy. These surveys are set
to dominate the feld over the next decade.
Professor Bland-Hawthorns work is described
in the pre-eminent review journal, the Annual
Reviews of Astronomy and Astrophysics (in
2002 and 2005). He has also helped to develop
the science case for the GAIA satellite to be
launched in 2011 that will measure positions
and three-dimensional space motions for a bil-
lion stars in the next decade.
A parallel theme of his research is the accretion
and ejection of gas in the vicinity of galaxies.
He frst showed that the mysterious high-ve-
locity clouds are actually close to us and quite
low mass, which means they cannot account
for the gas apparently missing in the Galaxy, as
was widely believed. He demonstrated that the
Magellanic gas stream is rapidly dissolving and
raining gas into the Galaxy. Over two decades,
he has demonstrated that both starburst and
black-hole galaxies generate huge energetic
winds that carry gas, metals and energy far
from galaxies.
Complementing this astrophysical research, he
has been actively exploring new instrumenta-
tion. Most recently he has led developments in
astrophysics, exploiting optic fbre technology
in new astronomical instruments. These revolu-
tionary technologies will be used to search for
the frst galaxies in the early universe, and the
existence of cosmic antimatter.
Professor Benjamin Eggleton
Professor Eggleton is Director of CUDOS
and also heads the newly formed Institute of
Photonics and Optical Science (IPOS) at the
University of Sydney. He is regarded as a world
leading researcher and pioneer in the felds of
optical physics and photonics, which is the
use of light for the transmission and process-
ing of information. Professor Eggleton has
pioneered fundamental studies in the optics of
man-made nanostructured optical materials,
known as photonic crystals and his research
has led directly to the realisation of new optical
devices for telecommunications applications.
His current research focuses on the develop-
ment of the ultrafast photonic chip, a crucial
device for the development of next generation
communication systems. In this context, his
team has reported numerous breakthroughs,
including demonstrating that the speed of light
ARC
Federation
Fellow
Joss Bland-
Hawthorn
222
|
Genes to Galaxies
could be slowed down and that slow light can
be harnessed for effcient nonlinear processes.
His team recently demonstrated switching of
optical signals at 640Gb/s (i.e. 640 thousand
Megabits per second) in a monolithic glass
device. This is about 60 times faster than the
switches currently in Australias telecommuni-
cation networks.
Professor Bryan Gaensler
A remarkable discovery made by 20th century
astronomers was that the Universe is magnetic.
These cosmic magnetic felds play a vital role
in controlling how stars and galaxies form and
evolve. This naturally occurring magnetism also
regulates solar activity, protects the Earth from
harmful particles, and is vital for the navigation
of birds and other species. However, despite
the ubiquity of astrophysical magnets, we do
not understand what creates them, or how they
have maintained their strength over billions of
years. And unfortunately, magnetic felds are
invisible even to the largest telescopes.
Professor Bryan Gaensler is working to open
the window to this Magnetic Universe by
exploiting an effect called Faraday rotation, in
which light from a background object is subtly
changed when it passes through a cloud of
magnetised gas. He and his team are carrying
out detailed measurements using radio tele-
scopes in Australia and in the USA, with which
to measure the Faraday rotation in the emission
from thousands of distant galaxies. With these
measurements, magnetic felds are detected
throughout the Universe. The observations they
are undertaking result in three-dimensional
maps of cosmic magnetism, which are reveal-
ing what these magnets look like and what role
they have played in the evolving Universe.
9000 light years
Research at the School of Physics
|
223
Professor Peter Robinson
Professor Peter Robinson carries out research
in two main areas within the feld of Complex
Systems. In theoretical plasma physics he stud-
ies random and nonlinear processes for appli-
cation to both space and laboratory plasmas. In
biological physics, he studies the dynamics of
brain activity and measurements, with applica-
tions in neuroscience, sleep research, imaging,
and medicine.
What does the future hold
for the School of Physics?
The priority for the School is excellence in re-
search and teaching and to continue to improve
our performance in both areas. We are also
committed to raising the awareness of science
in the community. We have several outreach
programs to encourage science awareness and
to provide training and resources for science
teachers. One of the most exciting programs in
the Faculty of Science is the Talented Student
Program, which offers a research experience
and individual challenges for the most gifted
students entering University. Physics is proud
to be a part of this program and we encourage
these students to continue on to postgraduate
studies. However, we are also committed to
giving all our students an enriching experience
in the School of Physics.
One initiative we are developing is a suite of
postgraduate coursework programs, such as
the successful Master of Medical Physics, which
was begun in 2004. By 2010 we shall have two
other programs in place, in Applied Nuclear
Science and Optics and Photonics. These pro-
grams have links with professional placements
in industry and hospitals. Other areas being
considered are space science and astronomy.
These programs complement the postgraduate
research degrees as part of the wide-ranging
experience of studying in the School of Physics.
High quality research demands top quality fa-
cilities, particularly in experimental disciplines
where laboratories need to be increasingly
sophisticated to support cutting edge science.
High performance computing and vast data
storage capabilities are required for modelling
and simulations. To this end, a new building
for the School of Physics is being planned,
with teaching spaces for innovative learning
techniques, nanofabrication facilities, and
clean rooms to support a growing experimental
capability in the areas of photonics, quantum
science and applied physics. Our goal is to be-
come the acknowledged top School of Physics
in Australia and the region. We would be very
pleased to welcome any ISS scholars to this ex-
citing environment to study the laws of nature
and the world around us.
224
|
Genes to Galaxies
The International Science School (ISS) was estab-
lished by Professor Harry Messel AC CBE in 1962
to recognise and reward talented senior high school
students, and to encourage them to pursue careers
in science. The ISS is a two-week, fully residential
program of lectures, workshops, tours and special
events - and it is all free to the participating scholars.
Thus each scholarship is valued at around A$3000.
Alumni of the International Science School can be
found in senior positions in all walks of life, with
many of them acknowledging that their Science
School was responsible for changing their lives, and
recalling its two weeks as an exciting developmental
experience.
The International Science School, renamed the
Professor Harry Messel International Science School
in 1999 to honour Harry for his foresight, have con-
tinued uninterrupted for almost 50 years. In order to
ensure the continuation of the International Science
School, so that future students may also beneft,
the Science Foundation for Physics established The
Messel Endowment. The Foundation aims to raise
$5Million in 2009 Australian dollars. At the time of
printing, the fundraising campaign has come a long
way: in 2009, the Endowment sits at $3.1Million.
Despite this success, for which we are enormously
grateful, the Endowment still has a long way to go,
and the Foundation is determined to achieve the
target.
The Messel Endowment is managed so that the
real value of the capital is preserved. Bequests will
also be sought to ensure the growth of the capital
in the years to come. The primary purpose of the
Endowment is to support the International Science
School. If income from the Endowment exceeds the
requirements of the Science School the funds may,
with the approval of the Science Foundation, be
used to support other initiatives named to honour
Professor Harry Messel. Examples of such initiatives
may include a Professor Harry Messel Visiting Chair
and a Professor Harry Messel Lectureship.
As acknowledged with gratitude in the front of this
book, many individuals and companies have already
contributed to The Messel Endowment, and the
2009 Professor Harry Messel International Science
School has received considerable beneft from
the Endowment. All our Endowment donors are
acknowledged on our web site and in all books of
the lectures presented at future International Science
Schools, and on a permanent display in the School
of Physics.
We hope you have enjoyed your time at the
International Science School, or had your mind ex-
panded by reading the chapters submitted by the ISS
lecturers and their on-line podcasts. Many people,
after experiencing the ISS, wish to give something
back, but are not sure how to do this. Here are some
suggestions. First, you could consider coming back
as staff for the next International Science School.
There is information in the Scholar Handbook on
how to apply. Secondly, you could approach some-
one in your neighbourhood, for example a company
or philanthropic institution or even a member of
your family with the capacity to contribute, to seek
a donation for The Messel Endowment. A personal
approach is always the best method of obtaining
such support and a person such as yourself, who has
just benefted from an International Science School,
makes the best ambassador.
Finally, we realise that you may not be in a position,
at present, to give to the Endowment yourself
however, at some stage in the future, if you are in a
position to do so, we ask that you consider it then.
A donation form has been included on the next page
to assist you if you choose to proceed with some of
these suggestions. More donation forms are available
from The Messel Endowment at www.physics.usyd.
edu.au/foundation/
A contribution of A$30,000 to The Messel
Endowment will ensure the participation of one
student in perpetuity.
Please join us today in our vision for the young
scientists of tomorrow through The Messel
Endowment.
Help us to Honour Excellence
Professor Anne Green
Director, Science Foundation for Physics
A contribution of A$30,000 to The Messel Endowment will
ensure the participation of one student in perpetuity ...
ISS 2009
|
225
Science Foundation
for Physics
Gift Form
PERSONAL DETAILS
Title: Mr Ms Mrs Miss Dr Other________________________
First name/s: Last Name:
Mailing Address:________________________________________________________________________________________
City: State: Post Code:
Country: Phone Home: ( )
Phone Business: ( ) Email:
GIFT DETAILS
Please accept my gift of $
The gift is to be used for the following:
Gifts are tax deductible
PAYMENT DETAILS
Cheque (make payable to The University of Sydney, Science Foundation for Physics)
Credit Card: Visa MasterCard American Express Diners Club
Card No:
Expiry Date: / Cardholder Name:
Signature:
I would like my gift to remain anonymous
Please send me information about the Science Foundation for Physics
I am interested in receiving information about making a bequest to the Science Foundation for Physics.
You can make your gift on-line go to www.usyd.edu/gift
Thank you for your generous support
Please return this form to: Science Foundation for Physics
School of Physics (A28)
The University of Sydney, NSW 2006 Australia
Phone 61 2 9036 5194 Fax 61 2 9351 7726
ABN: 15211513464 Charitable Fundraising No: 10369
PRIVACY ASSURANCE: The information you provide on this form is collected by the University of Sydney to maintain contact and keep you up-to-date
with information about the University, its services, events and achievements. It may be passed on to groups affiliated with the University, such as alumni
organisations and foundations (local and overseas), SU Sport and residential colleges. Your name may be published in the annual honour roll. If you wish to
remain anonymous or do not wish to receive information, please contact Advancement Services (fax 9351 5688, or email alumni@vcc.usyd.edu.au).
The University abides by the NSW Privacy and Personal Information Protection Act".