SC 206 BREAKTHROUGHS IN SCIENCE

2014

OCTOBER 16, 2015

JOHN BUSH

EDITORS OF SCIENCE

EDITOR IN CHIEF

Marcia McNutt 2013-2016?

WHAT IS A BREAKTHROUGH?

Any development reported in a peer reviewed journal that the editors of Science consider to be of outstanding importance

SOME FORMER “BREAKTHROUGHS” • 2012

– Discovery of the Higgs Boson – A home run for ancient DNA

• 2013 – Cancer immunotherapy – Genetic microsurgery for the masses

THE HIGGS BOSON

• The “breakthrough”?: Experimental confirmation of the existence of a particle with properties consistent with theory

• What is the Higgs Boson?: An elementary particle—a disturbance in the Higgs Field

• So what?: If there were no Higgs Field the Standard Model would have to be rethought

SEQUENCING ANCIENT DNA

• The “breakthrough”?: Method for highly precise sequencing of ancient DNA

• Builds on high throughput techniques used to sequence modern DNA

• So what? Enables determining detailed genetic information about extinct hominins

GENUS HOMO

• One survivor plus many that are now extinct – Homo sapiens sapiens (modern human)* – Homo sapiens Neandertalensis (neanderthal)* – Homo sapiens (?) Denisova (Denisovans)* – Homo floresiensis (“Hobbit”) – Red Deer Cave people

• Interbreeding has occurred among them *DNA sequenced

SOME FORMER “BREAKTHROUGHS” • 2012

– Discovery of the Higgs Boson – A home run for ancient DNA

• 2013 – Cancer immunotherapy – Genetic microsurgery for the masses

CANCER IMMUNOTHERAPY

• The “breakthrough”: Successfully directing the human immune system to control or eliminate the spread of cancer

• Achieved by a number of techniques several of which have resulted in successful clinical trials

• So what? Provides an entirely new approach to treating cancer that augments surgery, radiation, and drugs

A SUCCESSFUL WEAPON AGAINST CANCER

• At least three FDA approved drugs – Apparently complete remission in some cases – Ineffective in other cases

• Research focus—to identify patient-treatment combinations that will be effective

GENETIC MICROSURGERY

• The “breakthrough”?: A new, relatively easy and rapid technique for specifically modifying double stranded DNA sequences

• CRISPR combines a DNA-cleaving enzyme with a short RNA molecule that is tailored to recognize specific nucleotide sequences

• So What? The new technique is fueling a “boom” in genome engineering and synthetic genomics

CONCERNS ABOUT CRISPR

• It is too easy—CRISPR kits can be purchased www.clontech.com/CRISPR

• It is too powerful—inheritable alteration of the human genome has been accomplished

• It is unregulated--there are no accepted guidelines or restrictions on the application of CRISPR

SCIENCE 2014 BREAKTHROUGH AND ALSO RANS

1.Comet rendezvous(3) 2. Cooperative ‘bots’ don’t need a boss 3. The birth of birds 4. Youth serum for real? (2) 5. Chips that mimic the brain 6. Cells that might cure diabetes (4) 7. Europe’s cave art has a rival 8. Giving life a bigger genetic alphabet (1) 9. Manipulating a memory 10 The rise of the Cube Sat

BREAK THROUGH CATEGORIES • Technology

– Landing on a comet – Rise of the Cube Sat – Robots that cooperate – Chips that mimic the brain

• Medical therapy – Young blood fixes old – Cells that might cure diabetes

• Knowledge/Technique – Enlarging the genetic alphabet – Manipulating memories – The birth of birds – Asian cave art

FOR EACH “BREAKTHROUGH” A SUMMARY SLIDE

• What is the “breakthrough”?: • How was it achieved?: • So what?:

SCIENCE AND TECHNOLOGY BREAKTHROUGHS

“The scientist discovers that which exists. An engineer creates that which never was.”

Theodore von Kármán

RENDEZVOUS WITH A COMET • The “breakthrough”: European Space Agency mission

to comet 67/P Churyumov-Gerasimenko • Culmination of the Rosetta mission--an ESA program

initiated in the 1980s • So What?

– The first spacecraft to orbit and then accompany a comet toward the sun

– The first spacecraft to land instruments on a comet – Expect to answer questions about the formation of solar

system and particularly about the history of the Earth.

COMET 67P CHURYUMOV-GERASIMENKO

THE ROSETTA MISSION • Planning began in the early 1980s • ESA initiated Rosetta program in 1993 • The spacecraft, instruments, and launch

vehicle were designed and built in Europe • Launched on March 2, 2004 • Put in “hibernation” from June 2011 to

January 2014 • Achieved orbital insertion around 67P on

August 6, 2014

ROSETTA TRAJECTORY

ASTEROID 2867 STEINS

ASTEROID LUTETIA

EUROPEAN SPACE OPERATIONS CENTER DARMSTADT, GERMANY

WHAT QUESTIONS MIGHT BE ANSWERED?

• What are comets made of and how did they form?

• What happened in the early stages of the formation of the Solar System?

• What can we learn about the evolution of the Solar System?

• Did comets bring water to Earth? • What role, if any, did comets play in the origin

of life on Earth?

THE PHILAE LANDER

WHAT HAVE WE LEARNED FROM PHILAE?

• Communication between Philae-Rosetta 60 hr

+5 1/2 min • Surface of 67P is inhomogeneous • Several organic compounds were found that

never before were detected in comets • Water/ice of 67P has a different isotopic

composition from Earth’s

WHAT ARE WE LEARNING FROM ROSETTA?

• 67P has weather (of a sort) • 67P was formed by joining two different

bodies • 67p erupts “geysers” of water vapor and dust

WHAT MAY WE LEARN?

• Right now Rosetta is tracking changes in 67P as it begins to move away from the Sun

• Still early days: Rosetta mission has been extended to September 2016

A “GOLDEN ERA” OF EXPLORATION? • Pluto (dwarf planet) • Ceres (dwarf planet) • Europa (moon of Jupiter) • Ganymede (moon of Jupiter) • Callisto (moon of Jupiter) • Io (moon of Jupiter) • Enceladus (moon of Saturn) • Titan (moon of Saturn) • Dione (moon of Saturn) • 2014MU69 (Kuiper Belt object)

RISE OF THE CUBESAT • The “breakthrough”: Expanding use of small, low-

cost nanosatellites for a variety of scientific and commercial programs

• Cubesats are inexpensively launched, miniaturized satellites of standardized size that employ mostly off-the-shelf technology

• So what? – Enable high school and college participation in space

research – Provide opportunities to expand low earth orbit

surveillance – Potentially useful for extra terrestrial missions

A RECENT EXAMPLE

• October 8,2015 Vandenberg AF Base • Participants: Aerospace Corporation, AMSAT,

Salish-Kootenai College, University of Alaska Fairbanks, US Army, JPL, SRI, Tyvak Nanosatellites, Naval Post Graduate School, Cal Poly SLO

• Government Rideshare Advanced Concepts Experiment (GRACE)

GRACE TEAM

GRACE

• Thirteen Cube Sats in eight deployers • Attached to bulkhead of an Atlas V Centaur

rocket

ALASKA RESEARCH CUBESAT • Designed, built, tested, and operated by students • Education mission objective: Provide authentic,

hands-on student experience • Science mission objectives

– Characterize the thermal and vibration environment inside the launch vehicle

– Validate a novel attitude control and determination system – Validate a high bandwidth communication system by

obtaining images of changing snow and ice coverage in arctic regions

ROBOTS THAT COOPERATE AUTONOMOUSLY

• The “breakthrough”: Multiple demonstrations of groups of robots that coordinate their movements without centralized direction

• Achieved by designing hardware and software to sense, communicate, execute and control motion based on local information

• So What: may lead to the development of fully autonomous groups of robots: self organizing vehicle traffic, self directing military and police operations, self organizing warehouse operations….

CAN A THOUSAND SWARMNG ROBOTS OUTSMART NATURE?

VIDEO

ARTIFICIAL INTELLIGENCE • “The science and engineering of making

intelligent machines” John McCarthy 1955 • An intelligent machine “perceives its

environment and takes actions that maximize its chance of success”

• Goals: Machines that display – General intelligence—”strong AI”? – “Weak AI”-- Reasoning, planning, learning,

processing natural languages, perceiving their environment, accessing knowledge as needed, moving and manipulating objects

SOME AI EXAMPLES

• Expert systems: medical diagnosis, evaluating mortgage applications…

• Recognition systems: e.g. Google and Facebook • Game playing programs e.g. Deep Blue • Robot controls e.g. Roomba • Personal assistants e.g. Siri • Question answering systems e.g. Watson • The AI Effect: “AI is whatever hasn’t been done yet”

HUMAN BRAIN

STRUCTURE OF THE BRAIN • Gross structure

– Forebrain: Cerebrum, Thalamus, Hypothalamus – Midbrain: Tectum, Tegumentum – Hindbrain: Cerebellum, Pons, Medulla

• Neuron: “an electrically excitable cell that processes and transmits information”

NEURONS

• Structure: cell body (soma), dendrites, axon • Synapses: junctions between axon and

dendrites • Myelin sheath: fatty layer around the axon

SOME BRAIN MAPPING PROJECTS

• Brain Activity Map Project funded by NIH • Human Connectome Project funded by NIH • Big Brain funded by EU • Allen Brain Atlas funded by the Allen Brain

Institute

CHIPS THAT MIMIC THE BRAIN

• The “breakthrough”: Commercial introduction of large scale “neuromorphic” chips designed to mimic operation of the human brain

• Result of convergence of brain research and hardware and software developments

• So What? Facilitation of applications of Artificial Intelligence

BACKGROUND • Computer chip designs based on von Neumann

architecture are inefficient dealing with sensory inputs – Recognizing – Acting – Learning

• Single chips and software designs based on the ideas of the way brains function have been built that can more efficiently accomplish these tasks

• Neuromorphic chips have been successfully integrated into large scale structures

BLUE GENE SUPERCOMPUTER

COMPUTER ARCHITECTURE

NEUROMORPHIC COMPUTING

• A design concept consistent with non-von Neumann and non-Turing computer architectures

• Accessible with available chip-making technology (CMOS)

• Features: universal, scalable, fault tolerant, efficient power use, speed, learning

NEUROMORPHIC CHIP

IBM NEUROSYNAPTIC CHIP

SOME DEVELOPERS

• IBM- “Truenorth” • University of Heidelberg • Intel • Qualcomm

IBM’S VISION

YOUNG BLOOD FIXES OLD

• The Breakthrough: a factor (GDF11)in the blood of young mice reverses some effects of aging in elderly mice

• The rejuvenation of elderly mice that results from sharing circulatory systems with young mice was traced to the concentration of GDF11 in the blood

• So What? Provides a target for drug development to produce the effects of “the fountain of youth”.

CONTROVERSY • The original research was reported by Amy

Wagers’ group at Harvard • In 2015 a research group at Novartis

challenged the Harvard research • The discrepancy between the results has not

been explained—but it looks bad for Wagers

“We remain convinced that at least one form of GDF11 declines in blood with age and that maintaining GDF11 levels in an appropriate physiological range is essential for muscle health.”

APPROACHES TO “THE FOUNTAIN OF YOUTH”

• Clinical trial of young plasma with Alzheimers patients

• Clinical trial of Metformin ? (A number of other drugs show positive effects in mice)

• Clearing the body of senescent cells • Inhibiting the transcription factor ATF4

CELLS THAT MIGHT CURE DIABETES

• The “breakthrough”: Methods for converting embryonic or pluripotent stem cells into cells that resemble human pancreatic β cells

• Established a “recipe” for converting human stem cells into cells that secrete insulin and share most of the properties of human β cells

• So What? Provides a possible basis for a cure of Type I diabetes

Cell, 159, 428-439, October 9, 2014

Cell, 159, 428-439, October 9, 2014

DELIVERY PROBLEM

• Type 1 diabetes is caused by destruction of β cells by the immune system

• How can the destruction of the artificial cells be prevented?

AN APPROACH

PHASE 1 CLINICAL TRIAL HAS BEGUN

SYNTHETIC BIOLOGY

• ‘Synthetic biology is the engineering of biology: the synthesis of complex, biologically based (or inspired) systems, which display functions that do not exist in nature.’

• Synthetic biology will enable the design of ‘biological systems' in a rational and systematic way’

• For what purposes?

ENLARGING THE GENETIC ALPHABET • The “breakthrough”: production of living cells that are based on DNA strands containing synthetic nucleotides • Standard techniques of genetic engineering

were used to incorporate synthetic molecules compatible with the double helix structure of DNA to create an unnatural lifeform

• So What?: Many potential consequences—none demonstrated as yet

POTENTIAL

• To enable the production of useful proteins • To contribute to understanding DNA function • To enable the creation of new life forms • To clarify the origin of life • But! The conditions for translating the

information in these unnatural DNA sequences into proteins are unknown

IS THIS SAFE?

UNNATURAL CELLS NEED A FRIENDLY ENVIRONMENT TO SURVIVE

MANIPULATING A MEMORY

• The “breakthrough”: specific memories can be implanted, removed or altered in emotional affect by stimulating specific groups of brain cells

• This has been accomplished by light activation of optogenetically labeled cells

• So What? A powerful technique for exploring memory; provides support for the Hebbian model of memory formation

OPTOGENETICS

• Based on genetically engineered DNA that can express a light sensitive protein linked to a gene encoding a yellow fluorescent protein

• The engineered DNA is inserted into cells to be studied (neurons for example)

• By modifying experimental conditions the study cell population can be manipulated

CREATING A MEMORY

REACTIVATING A MEMORY

CREATING A FALSE MEMORY

SO WHAT?

• Supports a physical basis of memory • Supports the Engram model of memory • Potentially provides a means to develop a map

linking brain structure to brain function • Therapeutic possibilities?

– Optogenetic techniques have been employed with non-human primates

– Not likely to be therapeutically useful for humans

THE BIRTH OF BIRDS

• The “breakthrough”: elucidation of the sequence and timing of the evolutionary steps linking extinct theropod dinosaurs to modern theropod dinosaurs (birds)

• Resulted from analyses of features from over 20 years of remarkable fossil discoveries

• So What? Provides a consistent description of the evolutionary sequence responsible for birds

THEROPOD DINOSAURS

TAXONOMY RANKED HIERARCHY

Human House sparrow • Kingdom Animalia Animalia • Phylum Chordata Chordata • Class Mammalia Aves • Order Primates Passeriformes • Family Hominidae Passeridae • Genus Homo Passer • Species Homo sapiens Passer domesticus

CLADE

A group of organisms that are lineal descendants of a common ancestor

TAXONOMY CLADISTICS

T. Rex House sparrow • Clade Dinosauria Dinosauria • Order Saurischia Saurischia • Suborder Theropoda Theropoda • Division Coelurosauria Coelurosauria • Infradivision Tyrransauroidea *Maniraptora • Clade Tyrranosauridae Aviale • Clade Tyrranasaurinae Aves • Genus Tyrranosaurus Passer • Species Tyrranosaurus rex Passer domesticus

EVOLUTION OF BIRDS

MANIRAPTOR: ALVAREZSAURIA

Shuuvia deserti

EVOLUTION OF BIRDS

PARAVES

Scansoriopteryx heilmanni Sinovenator changii

EVOLUTION OF BIRDS

AVIALAE: ANCHIORNIS

EVOLUTION OF BIRDS

AVIALAE: ARCHAEOPTERYX

EVOLUTION OF BIRDS

ENANTIORNITHES

Shanweiniao cooperorum Sinornis

ORNITHURAMORPHA GANSUS YUMENENSIS

ORNITHURAE: ICTHYORNIS

HOATZIN

ANDEAN CONDOR

HOUSE SPARROW

EMU

SOME MILESTONES

• Erect posture, bipedal gait 243 Ma • Wishbone, air-filled bones, nesting 231 Ma • Feathers, reduced size, larger cranium 165 Ma • Wings, pinnate feathers 160 Ma • Loss of hind wings, powered flight 140 Ma • Long keeled breast bone, beak, 131Ma modern tail feathers

REVERSING EVOLUTION?

THEROPOD DINOSAURS

EUROPE’S CAVE ART HAS A RIVAL

• The “breakthrough”: dates are established for figurative cave art in Indonesia that predates that in Europe

• Dates were established by dating speleothems associated with the art

• So What? Suggests that the artistic impulse was an attribute of homo sapiens prior to the dispersal from Africa

DATING CAVE ART

• Date charcoal using carbon 14 • Date rocks using uranium-thorium • Date using stylistic judgments

MAROS CAVES

CORALLINE SPELEOTHEMS: “CAVE POPCORN”

DATING SPELEOTHEMS • Uranium 238 uranium 234 • Uranium 234 thorium 230 ……

U234/U238

Th230/U234

MAROS CAVES

MAROS CAVE

FEMALE BABIRUSA

HOMO SAPIENS’ MIGRATIONS

• H. sapiens originates in Africa about 200,000 BP • H. sapiens migrates east about 75,000 BP • H. sapiens reaches South Asia about 50,000 BP • H. sapiens reaches Australia before 46,000 BP • H. sapiens reaches Europe about 43,000

BP • H. sapiens reaches East Asia before 30,000 BP • H. sapiens reaches S. America before 15,000 BP • H. sapiens reaches N. America about 15,000

BP

HOMO SAPIENS’ ART • Blombos Cave S. Africa Engraving** 70,000 BP • Pilbara region Australia Rock painting** ~50,000 BP • Maros Caves Indonesia Rock painting * 35*-40,000** BP • Gorham’s Cave Gibraltar Engraving** ~39.000 BP • El Castillo Cave Spain Rock painting** >40,800 BP • Chauvet France Rock painting* 35,000 BP • Geissenkösterle Germany Flute 40,000 BP • Hohle Fels Germany Sculpture* 40,000 BP • Stadel Cave Germany Sculpture* 40,000 BP *Figurative **Abstract

Blombos Cave Gorham’s Cave

EL CASTILLO CAVE

MAROS CAVE

CHAUVET CAVE

THE CAVE OF FORGOTTEN DREAMS WERNER HERZOG

SCULPTURE 40,000 BP

SOME ANSWERABLE QUESTIONS?

• Why did Homo sapiens engage in art? • Did Neanderthals create art? • Was the practice of cave art invented more

than once by Homo sapiens? • Did anatomical and behavioral modernity

develop in tandem? • How do you identify modern behavior?