[Catalyst 2019]

VOLUME 12,2019

RICE UNDERGRADUATE SCIENCE RESEARCH JOURNAL

CAR T-CELLS

the frontier of

oncology therapies

ALSO IN THIS ISSUE:

+Interconnection of Genetics & Behavior in Drosophilia

+Exploring the Response of PTSD to Psychotherapy

From the

EDITORS

Dear Reader,

Welcome to the twelfth annual edition of Catalyst, Rice’s premier Undergraduate

Science Research Journal. As a peer-edited publication written, edited,

and designed by undergraduate students, we are committed to fostering

interdisciplinary dialogue and championing scientific communication both inside

and outside of Rice. We seek to make science exciting, accessible,

and engaging for all of our readers, whether you be a scientist or a casual

enthusiast. In this year’s publication, you can find articles about fields ranging

from multi-domain artificial intelligence, to stem cell mobility, and post-traumatic

stress disorder.

This year, as an organization, Catalyst has expanded immensely in our goal

of improving scientific literacy and cultivating scientific dialogue across the

community. We have strengthened our connections with schools across Houston

as part of our mentorship and outreach initiative Eureka including incorporating

Catalyst Scientific Communication Section (CS^2). CS^2 was a pilot initiative in

which we brought Eureka students from Energy Institute to Rice’s Undergraduate

Research Symposium to present their AP Research results in the form of a

poster. In addition, the second issue of Catalyst Eureka was released and

distributed to students and teachers in our partner schools, members of the Rice

community, and professionals in the Texas Medical Center to much fanfare. On

Rice’s campus, Catalyst continued to lead at the university-wide level, organizing

the 2nd Annual Catalyst Fall Research Panel to help connect Rice undergraduates

to research opportunities. An improved format and schedule made the event

a huge success as more than 70 people attended. The year also witnessed an

improvement in our blogging platform Discoveries, with pieces on diverse topics,

scientific and otherwise, circulated frequently throughout the year among Rice

undergraduates.

The progress and expansion we have undergone this year would not have

been possible without the support of the Rice community, our partners, our

mentors, and our amazing staff. In particular, we would like to thank the Rice

Center for Civic Leadership, the Rich Endowment, the Program in Writing and

Communication, and the School of Natural Sciences for their continued generous

support of Rice Catalyst’s endeavors. We also want to especially thank Dr. Dan

Wagner, our faculty sponsor who has provided us with invaluable advice and

guidance throughout this entire process.

We are proud of how far Catalyst has come this year and we are excited for our

growth in the years to come. From the entire Catalyst staff, we hope you enjoy

our latest issue as much as we enjoyed making it!

Mahesh Krishna, Activities Chair and Co-President

Sanket Mehta, Editor-in-Chief and Co-President

2018 - 2019

Staff

CO - PRESIDENTS

Mahesh Krishna, Activities Chair

Sanket Mehta, Editor-in-Chief

EDITORS

ATTRACTIONS

Brianna Garcia

Laura Jabr

Sophia Chang

Laurel Chen

Sam Shzu

Sara Ho

Dora Huang

Katherine Cohen

Kelsey Sanders

Meredith Brown

Jackson Savage

Yunee Park

Jenny Wang

SENIOR DESIGNERS

Anna Croyle

Evelyn Syau

Kaitlyn Xiong

DESIGNERS

Minjung Kim

J. Riley Holmes

Nina Kumar

Yvonne Chien

Hoang A. Vu

Sarah Swackhamer

BLOGGERS

Monika Karki

Brianna Garcia

Natalie Gault

Aditya More

Lani DuFresne

FACULTY ADVISOR

Dr. Daniel Wagner

DIRECTOR OF DESIGN

Juliana Wang

EXECUTIVE EDITORS

ATTRACTIONS

BREAKTHROUGHS

CONNECTIONS

DISCOVERIES

TREASURER

Jack Trouvé

OUTREACH DIRECTOR

Shravya Kakulamarri

BLOG DIRECTOR

Nigel Edward

PODCAST EXECUTIVE PRODUCER

Nick Falkenberg

Web Developer

Preetham Bachina

Jenny Wang

Ruchi Gupta

Rachita Pandya

Jacob Kesten

Evelyn Syau

BREAKTHROUGHS

Adelle Jia

Ananya Subramanian

Preetham Bachina

Minjung Kim

Andrew Mu

Yvonne Chien

Sarah Swackhamer

CONNECTIONS

Natalie Gault

DISCOVERIES

Evelyn Syau

Nigel Edward

Abram Qiu

Krithika Kumar

Luke Cantu

Priscilla Li

Samantha Cheng

Jim Zhang

Ksenia Metruck

Preetham Bachina

Nikit Venishetty

Lisa Shi

2 | CATALYST

ATTRACTIONS

table of

CONTENTS

4

6

8

9

10

12

14

16

18

CANCER IMMUNOTHERAPY: A Look at the Frontier of Oncology Therapies | Joshua Anil

SPIX’S MACAW: From Big Screen to Endangered List | J. Riley Holmes

VIRAL HATE: Dispelling Viruses’ Bad Rep | Jim Zhang

SUPERINTELLIGENCE: Consequences of an Intelligence Explosion | Josh Engels

The WHERE, WHAT, & WHY of Modern Day Epidemics | Dora Huang

Engineering the SCALE OF LIFE | Hoang A. Vu

RIDING THE OCTO-HIGH: MDMA and Sociality in Octopus Bimaculoids | Kelsey Sanders

IT’S ALL IN YOUR BRAIN: The Neural Network of Chronic Pain | Tammita Phongmekhin

Racing towards the CURE FOR CANCER | Hannah Boyd

BREAKTHROUGHS

19

20

22

24

26

28

29

30

THE MITOCHONDRIA: More than Just the Powerhouse of the Cell | Tasneem Mustafa

FLIES ON THE PRIZE: Exploring the Interconnectedness of Genetics and Behavior in Drosophila

Melanogaster | Sarah Swackhamer

A NEW HOPE FOR PARKINSON’S DISEASE: Induced Neural Clearance | Luke Cantu

THE ORIGAMI OF LIFE: Uncovering the Mechanism of Protein Folding and Other Complex

Systems | NamTip Phongmekhin

DOWN TO THE NEURON: Micro-Methods of Measuring the Brain | Adelle Jia

Magnetic Cell Manipulation | Amna Ibrahim

DO YOU HEAR WHAT I HEAR? Hair Cell Regeneration in the Cochlea | Maia Helterbrand

THE HIPPOCAMPUS: Let’s Make Some Memories | Christine Tang

CONNECTIONS

32

MEDICAL MARIJUANA? MORE LIKE MEDICAL MDMA: Party Drugs and PTSD | Aruni Areti &

Jackson Savage

DISCOVERIES

36 PLANT COMMUNICATION: Silent but Not Invisible | Lani DuFresne

37 Dark Matter Mapping | Ksenia Metruck

38 HUMANS: Are We Really Just Crabby People? | Natalie Gault

CATALYST | 3

Cancer Immunotherapy:

A LOOK AT THE FRONTIER OF ONCOLOGY THERAPIES

T

hink back to your childhood visits to

the doctor. Filled with stickers,

measurements, and shots. Lots and lots

of shots. Mumps, measles, meningitis…

the list of immunizations goes on and

on. And while you may have dreaded

those shots, those treatments boosted

your immune system, helping you fight

disease and stay healthy. Well, those

immune-enhancing therapies may not

just be for childhood diseases anymore.

In a new field of research called

immunotherapy, researchers are

developing preventive and therapeutic

cancer treatments that enhance a

patient’s immune response.

In fact, you may have already received

one of these preventive treatments. If

you grew up in 21st century America,

you most likely received the Gardasil

vaccination as an adolescent. Gardasil

protects against the Human

Papillomavirus (HPV), but it also

protects against the cervical, anal, and

oropharyngeal cancers that HPV can

1

cause.

However, prophylactic vaccines like

Gardasil are only the tip of the

immunotherapy iceberg. Therapeutic

cancer treatments also harness the

power of immunotherapy in order to

improve outcomes for patients already

suffering from cancer. These treatments

are on the cutting edge of cancer

research, and in recent years,

researchers and clinicians have made

significant progress toward developing

and releasing these innovative methods.

According to the National Cancer

Institute, immunotherapy is “a type of

therapy that uses substances to

stimulate or suppress the immune

system to help the body fight cancer,

2

infection, and other diseases.” While

there are several types of cancer

immunotherapies, they generally

destroy cancer cells by specifically

training immune cells to recognize and

eliminate cancerous cells. For instance,

cancer cells often contain many unique

surface proteins. Scientists can often

use these identifying markers to train a

patient’s immune system to recognize

these markers and mount an immune

response. This can allow for a more

targeted approach, as immune cells only

attack malignant cells, while leaving

3

healthy cells alone. In contrast, more

indiscriminate approaches such as

chemotherapy can often harm healthy

cells as well as cancer cells. While

immunotherapy includes many

approaches, a few methods, such as

checkpoint inhibition and CAR-T cell

therapy, have cleared clinical trials and

are currently treating cancer patients.

One of the more notable forms of

immunotherapy is checkpoint-inhibition.

This treatment has recently advanced

out of clinical trials and gained FDA

approval, and the researchers who

By Joshua Anil

While there are several

types of cancer

immunotherapies, they

generally destroy cancer

cells by specifically

training immune cells to

recognize and eliminate

cancerous cells.

discovered its working principle were

awarded the 2018 Nobel Prize in

Medicine. Checkpoint-inhibition

treatments work by inhibiting the

interaction of proteins on the surface of

cancer cells with checkpoint proteins on

immune cells. Receptors on T-cells, a

common type of immune cell,

checkpoint-proteins serve as control

switches for the immune response,

preventing the over-stimulation of the

immune system. Proteins on healthy

cells can bind to these receptors and

deactivate an immune response.

However, cancer cells can also use this

technique to disguise themselves as

harmless. They often express the same

protein as healthy cells, which they then

use to bind to T-cells checkpoint

4

receptors, consequently avoiding attack.

In order to combat this deception,

several drugs use monoclonal

antibodies to interrupt the binding

between the T-cell receptor and the

antigen-presenting cell. Keytruda is a

drug that targets the interaction

between checkpoint protein

programmed cell death protein 1 (PD-1)

—a receptor on the surface of cytotoxic

T-cells—and its corresponding

programmed death ligand-1 (PD-L1)

—a protein on the surface of healthy

5

cells and many cancer cells.

4 | CATALYST

Keytruda contains a monoclonal

antibody that binds to PD-1, inhibiting

the checkpoint protein from interacting

with PD-L1, and preventing the cancer

6

from evading an immune response.

There are several other drugs similar to

Keytruda that target other proteins, with

many treatments treating a wide variety

of cancers currently in clinical trials.

However, these treatments do come

with risks, as they induce a general

immune response which may cause a

patient’s immune system to begin

indiscriminately attacking healthy as

well as cancerous tissue.

Another form of immunotherapy, CAR-T

Cell Therapy, takes a much more

targeted route to selectively destroy

cancerous cells. Similar to checkpointinhibition

therapy, this treatment also

takes advantage of T-cell and tumor-cell

protein interaction. However, while

checkpoint-inhibition therapy prevents

cancer cells from pretending to be

normal, CAR-T Cell Therapy programs T-

cells to recognize and destroy cancerous

cells. Checkpoint-inhibition therapy

prevents interaction between cancer cell

surface proteins and T-cells, while CAR-T

Cell Therapy trains T-cells to bind to

unique antigens on the surface of

tumors in order to destroy them.

Doctors remove T-cells from a patient

and then genetically alter those T-cells

through viruses to produce proteins

called chimeric antigen receptors or

CARs, which will target unique antigens

7

on the surface of cancer cells. Scientists

then grow these altered T-cells in a lab

before injecting them back into a

patient, where they can serve as a

targeted and upgraded form of their

own natural immune system. In contrast

to chemotherapy or radiation, which

require a schedule of treatments, only

one infusion of the T-cells is necessary.

Because the edited T-cells replicate with

their synthetic antigens still intact, CAR-T

represents a type of “living drug”: a

renewable treatment which continues to

reproduce. CAR-T is currently only

approved for the treatment of blood

cancers, but its targeted focus and

outcome improvement give it significant

potential for treatment of other cancers

in the future.

Scientists then grow

these altered T-cells in a

lab before injecting them

back into a patient, where

they can serve as a

targeted and upgraded

form of their own natural

immune system.

Immunotherapy is pushing the

boundaries of cancer care. By using a

patient’s own immune system as a

weapon against cancer, researchers are

looking at cancer treatment in an

entirely new light—and achieving

promising results. In addition to the

checkpoint inhibition and CAR-T

treatments mentioned in this article,

researchers are also developing and

testing several other techniques like

Adoptive T-cell therapy and multiantigen

therapeutic vaccines. Medical

8

research is a time-consuming process,

and there were surely be many

unforeseen roadblocks along the way;

however, this new immunological

approach to cancer care places us on

the path to the hopeful day where

cancer treatment may be no more than

a simple shot at your local drugstore.

WORKS CITED

[1] National Cancer Institute.

https://www.cancer.gov/publications/dictio

naries/cancer-terms/def/immunotherapy.

(accessed Oct. 5, 2018).

[2] Guo C. et al. Adv Can Res. 2013, 119,

421-475.

[3] American Cancer Society.

https://www.cancer.org/treatment/treatme

nts-and-side-effects/treatmenttypes/immunotherapy/immunecheckpoint-inhibitors.html.

(accessed Oct.

18, 2018).

[4] Dine J. et al. Asia-Pacific J. Onc. Nursing

2017, 4, 127-135.

[5] Raedler LA. Am. Health & Drug Benefits.

2015, 8, 96-100.

[6] Dana-Farber Cancer Institute.

https://www.dana-farber.org/cellulartherapies-program/car-t-cell-therapy/.


[7] Dana-Farber Cancer Institute.

https://www.dana-farber.org/cellulartherapies-program/car-t-cell-therapy/.


[8] University of Washington Cancer

Vaccine Institute.

https://depts.washington.edu/tumorvac/re

search. (accessed Dec. 27, 2018).

Icons made by Smashicon, Freepik, and

prettycons from Flaticon

Images from Wikimedia Commons

DESIGNED BY

Minjung Kim

EDITED BY

Sophia Chang

CATALYST | 5

SPIX’S MACAW

FROM BIG SCREEN TO ENDANGERED LIST

BY J. RILEY HOLMES

In 2011, the animated movie Rio captivated

audiences with the story of Blu, a Spix’s

macaw destined to mate with the last wild

female of his species. However, a new study

from BirdLife International listed the Spix’s

macaw as one of eight bird species recently

confirmed as extinct in the wild. 1

Little is known about the lives of Spix’s

macaws, as limited evidence exists in

scientific literature. First discovered in 1819,

Johann Baptist Ritter von Spix, a notable

German biologist, documented the “Little

Blue Macaw” in Bahia, Brazil. 3 Even after

its discovery, Spix’s macaw was considered

particularly rare, hardly seen by the local

population. In fact, Spix’s macaw was thought

to be extinct until 1986, when ecological

surveyors located three macaws near the São

Francisco river region. 2

In 1988, the International Union for

Conservation of Nature (IUCN) changed

the macaw’s status from “extinct” to

“threatened”. 2 The IUCN Red List assesses

the status of endangered plant and animal

species. To classify probability of extinction,

the IUCN studies geographic range and

population decline rate of a certain

species. After intensive regional

surveys, data about the number of

individuals or area their territory

occupies indicates probability of

extinction in the wild. The Red

List also factors in artificiallysupported

populations

and individuals held

in captivity. After

analysis, the IUCN

classifies the

species into

one of

several categories, ranging from “least

concern” to “extinct”. 4

In 1994, Spix’s macaw was classified as

“critically endangered”, indicating rapid

population decline and a high

probability of extinction. 2

Less than fifty individuals,

captive and wild,

constituted Spix’s

macaw population. 4

Conservation efforts

were already

underway—

in 1995, a captive

individual was

reintroduced to the

wild. A couple of weeks

later, however, the

individual disappeared,

and researchers suspected

collision with a nearby

powerline. 2

Afterward, the only known remaining Spix’s

macaws existed in captive populations,

thought to be the offspring of the wild birds

spotted in 1986. 3 However, since not all

potential habitats were surveyed, the

IUCN could not officially declare

Spix’s macaw as Extinct in the Wild.

A rare sighting in 2016 raised hopes.

In Bahia, Brazil—the macaw’s native

region—a local farmer spotted a

blue bird flying over the forest along

the riverbank. The Society for the

Conservation of Birds in Brazil (SAVE

Brazil) later confirmed the sighting of

a Spix’s macaw. 5 However, hope of

a wild Spix’s macaw population was

fleeting. Given the large presence of

conservation groups in the area, many

believe the bird was just an escapee

from captivity. 1

In September 2018, a new study investigated

the Red List status of 51 “Critically

Endangered” bird species. Conducted

over eight years, this robust reassessment

analyzed previous survey records and

quantified the intensity of threats. The

study suggests five birds, including Spix’s

macaw, should be reclassified as “Extinct

90% of

bird extinctions in

recent centuries have

been species native to

islands.

in the Wild”. Another Brazilian parrot, the

Glaucous macaw, also spearheaded this list

as last sighted in 1998. The New Caledonian

Lorikeet and Pernambuco Pygmy Owl were

last sighted in 1987 and 1994, respectively.

Three species were also recommended

for reclassification as “Extinct”,

including the Cryptic Treehunter

and Alagoas Foliage-Gleaner.

A native Hawaiian bird, the

Poo-uli, has neither been

spotted in the wild nor

held in captivity since

2004. 1

Of the eight bird species

primed for extinction, five

are native to the South

American continent, and

four from Brazil specifically. 1

Dr. Stuart Butchart, BirdLife

International’s Chief Scientist,

highlights the concerning trend among

the study’s results. In recent centuries, 90%

of bird extinctions occur within species native

to islands. However, a “growing wave of

extinctions sweep[s] across the continents”. 1

The suspected cause of these extinctions?

Habitat loss.

When mainland extinctions outpace island

ones, conservationists must consider

the effect of human developments on

natural environments. Construction of the

Sobradinho hydroelectric dam in the 1970s

wiped out forests near Bahia, Spix’s macaw’s

native territory. 2 Birds in other regions of

Brazil and South America also experience

the effects of deforestation. Unsustainable

logging and agriculture directly contributes

to the population decline of these birds. 1

Given high deforestation rates among

these countries, this correlation is not

surprising. While habitat loss presents the

most prominent threat, illegal trade also

encourages trapping and smuggling of

rare birds, consequently decimating wild

populations. 3

Though these statistics seem dismal,

conservationists remain optimistic for the

Little Blue Macaw. Sixty to eighty Spix’s

macaws still live in captivity, and on-site

6 | CATALYST

Pernambuco Pygmy Owl

Pernambuco

Alagoas Foliage Gleaner

Alagoas

Cryptic Treehunter

Alagoas

Spix’s Macaw

Bahia

Glaucous Macaw

Southern Brazil

Four Birds

listed in Birdlife

International’s

Study are native to

Brazil.

conservation activities promote their

survival. 1 In partnership with the Brazilian

government, the Association for the

Conservation of Threatened Parrots (ACTP)

aims to reintroduce Spix’s macaw into the

wild by 2021. 3 Various breeding programs

aim to increase Spix’s macaw’s base

population for a sustainable reintroduction.

Thirty-three Spix’s macaws have been bred

at the Al Wabra Wildlife Conservation and

Preservation Organization in the recent

decade. 6 The Brazilian Spix’s breeding

program and the ACTP’s German facilities

partner to regularly exchange offspring

to broaden genetic diversity

within the captive species,

as inbreeding can lead to

harmful genetic defects.

ACTP also collaborates

with universities and

research facilities to

explore possibilities

for artificial

insemination. 3

extinction

remains a prevalent

and frightening

possibility for this

species.

The ACTP also aims

to develop a suitable

and supportive habitat

for the reintroduction

of Spix’s macaw. After

intensive search efforts for

the optimal location, Concordia

Farm was purchased in Bahia, Brazil. The

Farm includes the land constituting Spix’s

macaw’s last wild habitat. 3 The land provides

a protective area for the reintroduction of the

Spix’s macaw, permitting further population

growth without external threats. Likewise,

education programs raise awareness and

teach the local population about the bird’s

importance. 3

Rio gave Spix’s macaw Hollywood fame, but

the challenge these birds face is anything

but fiction. As BirdLife’s study confirmed

in 2018, extinction remains a prevalent

and frightening possibility for this species.

Thankfully, multiple conservation practices

help reduce the Spix’s macaw chances for

extinction. Many other rainforest birds,

however, do not have this opportunity.

Unsustainable human activities, like

deforestation, abolish their habitats

and destroy their ecosystems.

As human influence continues

to expand, populations

must consider their

effect on local native

species. Greater

biodiversity influences

natural sustainability

and ecological balance.

Each species plays an

important role in its

ecosystem, as well as within

a society’s economic and

cultural identities. A society

that increases public ecological

awareness, codifies its conservation

efforts, and limits environmental destruction

can dramatically reduce a species’ chances of

extinction.

Works Cited

[1] Dale, A.; Spix’s Macaw heads list of first bird

extinctions confirmed this decade. BirdLife

International [Online]. 2018. https://www.birdlife.

org/worldwide/news/spixs-macaw-heads-list-firstbird-extinctions-set-be-confirmed-decade.

(Oct. 5,

2018).

[2] BirdLife International 2018. Cyanopsitta

spixii. The IUCN Red List of Threatened Species

[Online]. 2018. https://www.iucnredlist.org/

species/22685533/93078343. (Oct. 5, 2018).

[3] Spix’s Macaw - ACTP. https://www.act-parrots.

org/spixs-macaw/?lang=en. (Oct. 5, 2018).

[4] Dublin, H.; IUCN Red List of Threatened Species.

Encyclopedia Britannica [Online]. 2009. https://

www.britannica.com/topic/IUCN-Red-List-of-

Threatened-Species. (Oct. 5, 2018).

[5] Hurrell, S.; Spix’s Macaw Reappears in Brazil.

BirdLife International [Online]. 2016. https://www.

birdlife.org/americas/news/spix%E2%80%99smacaw-reappears-brazil.

(Oct. 5, 2018).

[6] Al Wabra Wildlife Preservation. http://awwp.

alwabra.com/?p=1054. (Oct. 5, 2018).

Design By J. Riley Holmes

Edited By Katherine Cohen

Images Courtesy of David Riaño Cortés and WIkipedia

Commons

Vectors Courtesy of Georgiana lonescu from The Noun

Project

CATALYST | 7

VIRAL HATE

By Jim Zhang

Dispelling Viruses' Bad Rep

iruses have been found to exist

alongside life since its very inception.

VThese small packets of genetic material

have no means to reproduce on their

own, but instead hijack the cells of specific

organisms to replicate using their molecular

machinery. This hijacking frequently results

in diseases, which are responsible for

anything from one’s annual encounter with

the cold and flu, to the development of

certain cancers.

Because of their capacity for harm, viruses

are looked upon in a profoundly negative

light. This label is not unreasonable: viruses

have been responsible for countless deaths

throughout history. However,

not all viruses are pathogenic.

Studies have

shown that

viruses, through their

infection, play a role in

driving evolution and

Their primary objective is to

replicate and reproduce,

not necessarily harm their

hosts. Studies have

shown that viruses,

through their infection,

play a role in driving

evolution and moderating

the biosphere. 1 Their means

of doing so arise with the

various possible outcomes of

viral infection: hosts are killed immediately,

later, or never, as some viruses effectively lie

dormant within or across lifespans.

moderating the

biosphere.

In terms of evolution, certain infections

allows for viral genomes to be inherited

with the host’s offspring. Over time, this

occurrence can have profound impacts on

a species’ development across generations.

Specifically in humans, viruses are

responsible for over 8% of our genome. 2 This

8% encodes for countless critical proteins

responsible for how humans presently

function on a biochemical basis. For

example, within pregnant mothers, a protein

known as Hemo is produced by both embryo

and parent. Hemo comes from one of many

virally-originated genes, activating during

pregnancy to, as research suggests, assist

with embryonic development. Selection

has favored for its preservation, ensuring

continued survival of the viral genome

as it is duplicated and inherited across

generations. 1

The viral contribution to evolution cannot

be denied, demonstrating that they are

more than just simple agents of disease.

However, the sheer extent and range of this

evolutionary role remains uncertain. How

can viruses spread through mechanisms

other than infection? Recent studies have

shown that up to 800 million viruses are

“rained down” upon each square meter

of the planet’s surface. These viruses are

mostly found within the oceans. 3 There,

viruses assist in moderating the ecosystems

of the seas. Near the water’s surface,

there is an immense diversity of various

microscopic species. Each of these

species performs a niche, or purpose,

forming relationships not unlike

that of macroscopic terrestrial

ecosystems. Here, viruses act

as highly specific predators,

infecting strains of bacteria,

algae, and plankton to regulate

their populations and release

their sequestered nutrients back

for further use. Some estimates

show that, within the oceans, up to

1023 viral infections occur per second,

eliminating up to 20-40% of all bacterial cells

per day. 4

As moderators, viruses have also been

shown to assist with controlling algal

blooms, an issue becoming ever-prevalent

with increasing agricultural run-off. In many

cases, virus populations were found to

quickly eliminate overgrowing algae through

infection. 5 In doing so, these viruses prevent

the hypoxic dead zones and toxins algal

blooms would otherwise release, proving

vital for surrounding marine ecosystems.

Viruses have settled into incredibly diverse

ecological niches, maintaining a global

presence in their host organisms, marine

environments, and even the air we breathe.

Viruses frequently find themselves swept

into the air, either in dust or with the sea

foam, allowing easy travel through the

planet’s airstreams to circulate the globe.

This forms what has been referred to as

the planet’s “virosphere.” 1 The virosphere

allows otherwise-foreign genetic material to

cascade down to various ecosystems, with

one study noting it essentially “provides a

seed bank that should allow ecosystems to

rapidly adapt to environmental changes.” 3 In

other words, these viral showers introduce

potential new genes to be integrated into

new host species, potentially impacting how

said species will evolve.

Each of these studies and phenomena

demonstrate that viruses overall possess

an immense ability to not only spread

across ecosystems, but also moderate

their immediate and future populations

through infection and potentiallybeneficial

introduction of genetic material.

Researchers, recognizing these abilities, have

called for further research into the complex

roles viruses play in ecology. 6 The overall

impact of viruses across the evolutionary

ages is, for the most part, still unknown.

However, the potential these infectious

agents possess in influencing both the

planet’s immediate and long term future

demonstrates that viruses are much more

than simple, pathogenic particles. They

serve not only as drivers of evolution, but

moderators of ecosystems - much more than

simple agents of disease.

Works Cited

[1] Robbins, J. Trillions Upon Trillions of

Viruses Fall From the Sky Each Day. The

New York Times, Apr. 13, 2018. https://www.

nytimes.com/2018/04/13/science/virosphereevolution.html

(accessed Dec 13, 2018).

[2] Griffiths, D. J. Genome Biol. 2001, 2,

REVIEWS1017.

[3] Reche, I. ISME J. 2018, 12, 1154-1162.

[4] JOUR. Nat. Rev. Microbiol. 2011, 9, 628.

[5] Lehahn, Y. Curr. Biol. 2014, 24, 2041-2046.

[6] Weitz, J. S. et al. Unveiling the Viral

Ecology of Earth. Nautilus, Jun. 2017. http://

alliance.nautil.us/article/219/unveiling-theviral-ecology-of-earth

(accessed Dec. 13,

2018).

Design by Anna Croyle

Edited by Jackson Savage

8 | CATALYST

Superintelligence:

Consequences of an Intelligence Explosion

By Josh Engels

Artificial intelligence is slowly becoming

more prevalent in modern life. While

field-specialized artificial intelligences

are becoming more and more

common, each only reaches superiority

in one area, so their “takeover” remains

slow and controlled. Currently, no one yet

questions the superiority of the biological

mind as a whole, with its problem solving,

planning, and creativity unmatched by any

computer today. However, with the fast pace

of technological advancement, the balance

may soon tip in favor of the novel idea of

superintelligence, and perhaps sooner than

many think.

“Superintelligence” is the name for a

hypothetical intelligence that is superior

to humans in every field .1 It is an entirely

different idea from the current domainspecific

AIs. When such an entity arises, it

will by definition be better than humans

at everything, including the specific but

important skill of programming artificial

intelligences. The superintelligence could

therefore autonomously program an

even smarter AI, continuously replicating

this procedure, leading to an intelligence

explosion termed the “singularity” .2 We must

be extraordinarily careful in starting such an

explosion, for while the potential benefits

from an incredibly smart superintelligence

are extraordinary, so are the dangers.

In fact, the dangers are so extreme that

humanity could go extinct by accident.

Superintelligence does not have to be

programmed with evil intent in order for it

to have dire effects .6 The key issue is that an

AI may not have the same “obvious” ethics

governing its behavior as humans do.6

Consider an artificial intelligence created with

the goal of optimizing the creation of paper

clips, programmed by a team in a corporate

setting trying to get a leg up on competitors.

If this program achieves superintelligence by

editing its own code, it might determine that

the best way to optimize paper clips would

be to mass produce nanomachines and turn

the whole world into a giant computer. 7

It might happen in mere minutes; hence

the “explosion” moniker in the singularity

definition. It is tempting to think that a

superintelligence might develop a sense

of morality, and therefore not kill all life on

Earth, but there is no fundamental reason

for an intelligence to want to change its

goals unless it is programmed to do so. We

will have to ensure it has human ideas of

morality very carefully when programming it.

There are a couple feasible ways of

accomplishing this important goal. The

first is to emulate an entire human brain

and build a superintelligence from there,

knowing that human brains have human

values. In fact, we may already have the

necessary hardware; one estimate puts the

necessary number of computations per

second to simulate a brain at 1014, and our

best supercomputers are already faster than

this. 2 The road block is software: the human

brain is incredibly intricate, so mapping all

connections in order to create a simulation

is a very difficult problem. Thus, instead of

copying a human brain directly, multiple

projects are currently underway to model

human thought processes like reasoning,

reflection, and adaptation. 10 These projects

have an eventual goal of simulating an entire

human brain. 10

If we are successful

in the creation

of a friendly

superintelligence,

most of our

problems could be

instantly solved.

The alternative is to construct a

superintelligence from scratch and try

to assign it human values. For reasons

outlined in the paper clip example, this

approach is dangerous, but perhaps easier

to implement, making it a high priority

research area. Eliezer Yudkowsky, a

researcher working on how to prevent the

rise of superintelligence coinciding with the

downfall of humanity, has termed such a

superintelligence that would have humanity’s

best interests in mind a “Friendly AI”.8 He

is a part of MIRI, the Machine Intelligence

Research Institute, which ensures that the

creation of a superintelligence will have a

positive impact on humanity. 9 They conduct

research into how to create systems that we

can understand and prove are safe using

decision theory. 9 Instead of using a semi

random process akin to evolution with an

outcome we cannot directly control, they

seek to understand the theory behind the

way minds work. 9 Only then can we be sure

to create a Friendly AI.

It is difficult to determine exactly when

superintelligence will be developed; AI

researchers have historically been overly

optimistic about when smarter than human

intelligence will arise. 3 However, past

overconfidence has taught researchers the

significant difference between specific and

general artificial intelligence, so we should

pay attention to the fact that the median

response from experts attending the AGI-09

conference to the question “when will there

be a 50% chance of a superintelligence” was

20453, and that the response to the same

question about a 90% chance was 2100. The

consensus of those working on the problem

is that the creation of a superintelligence is

not one of science fiction.

With so many dangers and complications,

why even try to create a superintelligence

anyways? More so than any other technology

in the past, superintelligence will alter the

face of our society. If we are successful in the

creation of a friendly superintelligence, most

of our problems could be instantly solved.

With a being almost infinitely smarter than

us acting with our best interests at its heart

and nanotechnology at its back, poverty and

death will be a thought of the past. 6

WORKS CITED

https://nickbostrom.com/superintelligence.

html

http://consc.net/papers/singularity.pdf

https://sethbaum.com/ac/2011_AI-Experts.

pdf

https://nickbostrom.com/papers/survey.pdf

https://wiki.opencog.org/w/AGI_Projects

https://nickbostrom.com/ethics/ai.html

https://80000hours.org/articles/high-impactcareers/

http://intelligence.org/files/AIPosNegFactor.

pdf

https://intelligence.org/research/

https://arxiv.org/pdf/1610.08602.pdf

DESIGN BY Nina Kumar

EDITED BY Dora Huang

CATALYST | 9

AUTION CAUTION CAUTION CAU

CAUTION CAUT

The

Where

What

&Why

I

I had a little

bird,

Its name was Enza,

I opened the

window,

And in-flu-enza. 1

n 1918, children would sing this rhyme

while skipping rope, not knowing it’s

connection to the Spanish Flu, one

of the most deadly pandemics in world

history. 1,2 An epidemic is defined as the

sudden increase in the number of localized

cases of a certain disease, as seen in the

case of the bubonic plague, smallpox,

HIV/AIDS, and most recently with Ebola.

Pandemics, like that of the Spanish Flu, refer

to an epidemic that has spread all over the

world, affecting a large number of people at

a time. 3

In modern day, AIDS and Ebola are some

of the most dangerous and prevalent

epidemics that exist in the world and have

not yet been cured. In order to garner a

better understanding of epidemics and

how they appear and return, it is important

to analyze the impact that epidemics

historically have on society through the way

public health organizations have shifted in

the face of major disease outbreaks such as

Ebola and HIV/AIDS.

Most epidemics arise in the equatorial

region. This is due to the fact that tropical

regions are a hot zone for breeding

pathogens, especially those that are

transmitted through insects. The extreme

weather and heavy rains serve as a breeding

ground for mosquito-borne diseases.

Deforestation and the compounding

effects of climate change can also cause

the outbreak of disease by increasing the

likelihood of exposed pools of stagnant

and infected waters. 4 In comparison

with temperate regions, there is a higher

proportion of long-lasting immunity in

the temperate zones than in the tropic

regions. This can also be attributed to the

lack of health safety in many countries that

occupy the tropical region. Additionally,

animal reservoirs are more common in

underdeveloped countries in the tropics.

Therefore, animal-transmitted diseases are

also more common in the tropics than in

temperate regions. However, temperate

regions are more susceptible to diseases

that arise from domesticated animals, such

as influenza A, measles, and smallpox.

Most temperate diseases “are acute rather

than slow, chronic, or latent,” therefore the

host dies quickly, decreasing the radius of

infection among the population. As a result,

these acute diseases exhaust the population

of susceptible victims before it reaches the

state of being an epidemic. 5 Ultimately,

humans actively proliferate diseases by

engaging in unfavorable exchange with the

external environment. Through interacting

with invasive microorganisms that result in

unfavorable autoimmune reactions, humans

easily pass contagions along to each other. 6

Essentially, the tropics are a hotbed for

epidemic outbreak because of the climate

conditions, the human activities and

development in the region, and the types

of diseases that persist there. In examining

epidemics that arise from the tropical

regions and evolved into a worldwide crisis,

it is important to analyze the two most

It is important to

analyze the two

most modern cases:

the AIDS epidemic

and the Ebola

outbreak.

modern cases: the AIDS epidemic and the

Ebola outbreak.

The 1990s was known for its weird fashion

and technological breakthroughs but also

for the AIDS epidemic that targeted young

adults, especially members of the LGBTQ+

community. Originating in the West Africa

region, AIDS is defined as the most severe

phase of the human immunodeficiency

virus (HIV). HIV reduces the number of T

cells that help the immune system fight

infection, making a person more susceptible

to other infections or cancers. Over time,

HIV can destroy so many of these cells that

the body is completely vulnerable and even

the most benign illness can cause severe

damage. 7 This virus is contracted through

certain bodily fluids, and is most often

spread through sex or sharing needles. 8 The

current medicine that is used to treat HIV

Is antiretroviral therapy, which can greatly

prolong lifespan if taken every day. This is

not a cure, but it allows people diagnosed

with HIV to live nearly as long as people who

do not have it. 7

10 | CATALYST

TION CAUTION CAUTION CAUTION

of

Modern

Day

AUTION CAUT

Epidemics

By dora huang

The 2014 Ebola outbreak shattered news

headlines worldwide as it violently ravaged

the West African population. Many do not

realize that there is not just one Ebola virus,

but rather five, with four of the strains

causing severe illness in humans. Ebola

is the result of virulent transmission from

animal to animal, and later from animal to

human. Non-human primates are thought

to be the source of human infection,

however they are not the original source

(likely to be bats). 9 The largest outbreak

occurred in the West African region between

March 2014 and June 2016, but there have

been consistent small outbreaks since

then. Transmission occurs when bodily

fluids come into contact—whether it be

blood, secretions, or organs of an infected

person—which is why it is incredibly difficult

for doctors or researchers to study the

disease without getting infected themselves.

currently there

is no vaccine

or treatment

available for ebola

virus disease

Currently there is no vaccine or treatment

available for Ebola virus disease (EVD),

making it a present and imminent threat in

health and medicine. 9 In a report from the

World Health Organization (WHO) in October

2018, there is a total of 162 EVD cases in

seven different health zones. 10 Although EVD

is a lesser threat to well-developed nations,

as they simply instate policy to restrict travel

to and from the infected regions, it remains

a real threat to these underfunded and

unprotected regions of West Africa.

Ultimately, scientists continue to research

various ways to curtail modern day

epidemics. However, it also the duty of

the public to protect one another from

epidemics through receiving the appropriate

vaccinations and practicing general health

safety. Examining the modern AIDS and

Ebola epidemics and the ways medicine has

responded allows us to better understand

epidemic transmission. In the future,

researchers can adopt a more worldly

view on curing epidemics, combining new

technologies with public health services to

minimize mortality and risk for all people.

WORKS CITED

[1] Office of Public Health Scientific Services.

Principles of Epidemiology in Public Health

Practice, Third Edition. Centers for Disease

Control and Prevention [Online], May 18,

2012. https://www.cdc.gov/ophss/csels/

dsepd/ss1978/lesson1/section11.html

(accessed Nov. 2, 2018).

[2] Laino, C. Africa, the infectious continent.

NBC News [Online], November 4, 1999.

http://www.nbcnews.com/id/3072106/ns/

us_news-only/t/africa-infectious-continent/


[3] Centers for Disease Control and

Prevention. What are HIV and AIDS? HIV.

gov [Online], May 15, 2017. https://www.hiv.

gov/hiv-basics/overview/about-hiv-and-aids/

what-are-hiv-and-aids (accessed Nov. 2,

2018).

[4] U.S. Department of Health and Human

Services. The Basics of HIV Prevention.

AIDSinfo [Online], October 30, 2018. https://

aidsinfo.nih.gov/understanding-hiv-aids/factsheets/20/48/the-basics-of-hiv-prevention


[5] Georgetown University Health Policy

Institute. Issue Brief. [Online] 2003, 2.

https://hpi.georgetown.edu/agingsociety/

pubhtml/HIV/HIV.html (accessed Jan. 31,

2019).

[6] Public Health England. Ebola: overview,

history, origins and transmission. GOV.

UK [Online], December 15, 2017. https://

www.gov.uk/government/publications/

ebola-origins-reservoirs-transmission-andguidelines/ebola-overview-history-originsand-transmission


[7] Heymann, David L et al. Lancelot. 2015.

385(9980), 1884-1901.

[8] Carney, Timothy J et al. Amer. J. Pub.

Health. 2015. 1, 1740-1744.

[9] Disease Outbreak News. Ebola virus

disease – Democratic Republic of the Congo.

World Health Organization [Online], October

4, 2018. http://www.who.int/csr/don/04-

october-2018-ebola-drc/en/ (accessed Nov.

2, 2018).

[10] U.S. Department of Health and Human

Services. Ebola containment strategy

succeeding in Liberia. Centers for Disease

Control and Prevention [Online], Feb 20,

2015. https://www.cdc.gov/ophss/csels/

dsepd/ss1978/lesson1/section11.html

(accessed Jan. 31, 2019).

DESIGN BY Yvonne Chien

EDITED BY Kelsey Sanders

CATALYST | 11

Engineering The

SCALE

OF LIFE

By Hoang A. Vu

We continued

to develop our

microscopic

capacities

and can now

engineer

living

organisms that

can directly

impact our

daily lives.

The product of 4.5 billion years of

Earth existence is not simply a

linear sum of its 8.7 million living

species. Instead, those living species

are made up of complicated, interlinked

building blocks, each occupying a distinct

region on the hierarchical scale of life. 1,2

Despite persisting controversy about the

blurry distinction between living/non-living

entities, the scale of life is generally accepted

to start with atoms and molecules as the

smallest units. These microscopic units build

up subsequent levels - organelles, cells,

tissues, organs, organisms, populations,

communities, ecosystems and biomes -

ultimately forming the biosphere - Earth.

A higher level is more than the sum of

smaller levels, with emergent properties

defining each higher order. This collective

and growing relationship yields a vast

variety of lifeforms with mind-boggling

complexity. 3 Around the middle of this scale

of life—somewhere between the size of

miniscule atoms and massive biospheres—

lies one group of natural tinkerers. During

its relatively short time of existence, this

200,000-year-old species has interfered with

life at every level.

Now, picture the human race as a single

child: curious and naughty, but extremely

capable.

To ensure its survival, the child first meddled

with organisms its size on the scale of life. A

major turning point for the human race was

the transition from hunting and gathering

to farming during the Neolithic revolution

around 10,000 BCE. 4 This revolution signifies

humanity’s transition from simply interacting

with other organisms to actively engineering

them, examining, manipulating and even

creating entirely new varieties and breeds

of animals and plants. As humans gradually

improved, they fostered the ability to

engineer entire populations – a higher step

in the hierarchy of life. This could be shown,

for example, through the way human, over

the course of fourteen thousand years,

managed to domesticate wolves into docile

dogs as we know them today. 5

As the child became more excited to explore

the higher levels of this hierarchy, humans

began engineering whole ecosystems.

Starting with urbanization in the Uruk period

(4300-3100 BCE), humans began cutting

down trees, building dams and depleting

multiple sources of natural resources. 6 They

were altering, sometimes permanently, the

way many living organisms interacted with

their ecosystems.

The human narrative became more

fascinating and nuanced when the child

(after thousands of years of development)

realized it could meddle with things orders

of magnitude smaller than its size.

In early 1960s, the advent of tissue

engineering revolutionized human attempts

in manipulating nature; synthetic skin as

treatment for burn victims was among the

first application of the field. 7 Ever since

then, scientists have progressed from

recreating skin tissues to fabricating entire

artificial organs. Among the most recent

developments in the field, for example,

researchers such as Uygun B. and colleagues

from Harvard Medical School have

demonstrated application of decellularized

liver matrix to reengineer transplantable

liver graft. Despite many underlying

problems, these experiments show early

promise in solving the pressing shortage of

organ donations in the near future. 8

One step further down the scale, as

biomedical engineering shifted its focus

from tissue level to cellular and subcellular

levels, significant progress has been made

to add yet another tool into humankind’s

arsenal. Scientists can now engineer living

cells to manufacture desired products,

including biological substitutes such as

new bones. 9 This is made possible after the

development of cell culture technology,

which allows for the ability to grow living

cells under laboratory environment.

As time passes, the child improved at seeing

and manipulating incomprehensibly small

living things.

Lower on the scale of life, macromolecules

such as protein or DNA have become

prime targets for human to engineer new

properties to natural species. Genetic

engineering is one prime example where

genetic information is modified to produce

synthetic compounds. With the discovery

of DNA (by JD Watson and FHC Crick) and

subsequently recombinant DNA techniques

in 1972,10 scientists have come a long way

in the field of genetic engineering. From

the first genetically engineered, antibioticresistant

bacteria 1972, 10 we continued

to develop our microscopic capacities

and can now engineer living organisms

that can directly impact our daily lives.

These techniques are now well-applied,

such as in the application of recombinant

Adeno-associated virus (rAAV) that can be

programmed to target different organs for

gene delivery, or development of complex

synthetic DNA-based assays used in

infection detection and differentiation. 11,15

With the ongoing descent in scale that

human can manipulate, one of the most

groundbreaking lab instruments in

recent years was the scanning tunneling

microscope (STM). Humans are now

capable of manipulating atoms – the

smallest currently acknowledged level in

12 | CATALYST

the scale of life. Ever since Don Eigler’s

use of the STM to spell out the word “IBM”

with 35 xenon atoms, nanotechnology has

progressed drastically, promising nearfuture

applications. 12 One such application

arrived recently, when the same Eigler’s

group managed to construct an electrical

switch with a single atom as its moving

part, opening the gate to a brand-new

microscopic world. 12

At some point in time, the child delighted

in finding out that the way the scale of life

was set up allows it to manipulate elements

at the bottom of the scale to create rippling

effects at the biosphere’s level.

With the expanding toolbox, humans have

become extremely ambitious. Attempts are

now made at various levels to even engineer

a biosphere by controlling things at a lower

level in the hierarchical biosystem. At the

68th International Astronautical Congress,

SpaceX CEO Elon Musk spoke about his

plans for interplanetary travel and how he

firmly believed in humanity’s future as an

interplanetary species. 13 While at this point

in time, this claim sounds unrealistically

audacious, current efforts have shown early

potential in terraforming other planets.

As part of the international Genetically

Engineered Machine competition, a team

from Stanford and Brown University have

been engineering space-compatible bacteria

to acquire potentially useful functions, such

as produce cement-like material for building

or sugar for feeding other microbes. 14 There

is a long way before such a vision of planet

colonization can become a concrete plan,

but humankind might be further along than

anyone could have previously realized.

Regardless of the all-consuming ambitions,

human kind is still very much like a clueless

child – albeit alarmingly a well-equipped and

adaptive one. It is trying to wield whatever

tools available to solve its problems, trying

its best to avoid going down any irreversible

path. But at the end of it all, what it knows

is only a small fraction of the vast unknown,

and there is no external force to guide

it towards the correct path but its selfimposed

ethical rules. This emphasizes the

ever-important needs for proper regulations

and respect towards common standard

scientific protocols.

Works Cited

[1] Dodd et al. “Evidence for Early Life

in Earth’s Oldest Hydrothermal Vent

Precipitates.” Nature 543, no. 7643 (March

2017): 60–64. https://doi.org/10.1038/

nature21377

[2] “How Many Species on Earth?

About 8.7 Million, New Estimate Says.”

ScienceDaily. Accessed October 30,

2018. https://www.sciencedaily.com/

releases/2011/08/110823180459.htm.

[3] Novikoff, A. B. “THE CONCEPT OF

INTEGRATIVE LEVELS AND BIOLOGY.”

Science 101, no. 2618 (March 2, 1945):

209–15. https://doi.org/10.1126/

science.101.2618.209.

[4] Editors, History com. “Neolithic

Revolution.” HISTORY. Accessed January 31,

2019. https://www.history.com/topics/prehistory/neolithic-revolution.

[5] “How Animal Domestication Works.”

HowStuffWorks, April 14, 2008. https://

animals.howstuffworks.com/animal-facts/

animal-domestication.htm.

[6] “Urbanization.” Ancient History

Encyclopedia. Accessed October 10, 2018.

https://www.ancient.eu/urbanization/.

[7] Berthiaume et al. “Tissue Engineering

and Regenerative Medicine: History,

Progress, and Challenges.” Annual Review

of Chemical and Biomolecular Engineering

2 (2011): 403–30. https://doi.org/10.1146/

annurev-chembioeng-061010-114257

[8] Mazza et al. “Liver Tissue Engineering:

From Implantable Tissue to Whole Organ

Engineering.” Hepatology Communications

2, no. 2 (December 21, 2017): 131–41.

https://doi.org/10.1002/hep4.1136.

[9] Nerem, R. M. “Cellular Engineering.”

Annals of Biomedical Engineering 19, no. 5

(1991): 529–45.

[10] “Biotechnology Timeline: Humans

Have Manipulated Genes since the ‘Dawn

of Civilization.’” Genetic Literacy Project,

July 18, 2017. https://geneticliteracyproject.

org/2017/07/18/biotechnology-timelinehumans-manipulating-genes-since-dawncivilization/.

[11] Naso et al. “Adeno-Associated Virus

(AAV) as a Vector for Gene Therapy.”

Biodrugs 31, no. 4 (2017): 317–34. https://

doi.org/10.1007/s40259-017-0234-5.

[12] Ganapati, Priya. “20 Years of Moving

Atoms, One by One.” Wired, September

30, 2009. https://www.wired.com/2009/09/

gallery-atomic-science/.

[13] Musk, Elon. “Making Humans a Multi-

Planetary Species.” New Space 5, no. 2 (June

1, 2017): 46–61. https://doi.org/10.1089/

space.2017.29009.emu.

[14] “Team: Stanford-Brown - 2017.

Igem.Org.” Accessed October 30, 2018.

http://2017.igem.org/Team:Stanford-Brown.

[15] Crannell et al.. “Multiplexed

Recombinase Polymerase Amplification

Assay To Detect Intestinal Protozoa.”

Analytical Chemistry 88, no. 3 (February 2,

2016): 1610–16. https://doi.org/10.1021/acs.

analchem.5b03267.

Design By Hoang A. Vu

Edited By Katherine Cohen

CATALYST | 13

riding the

MDMA and sociality

Octopuses are generally regarded as

the most solitary species among

cephalopods.¹ As such, Octopus

bimaculoides normally would not

want to be anyone’s friend. This

octopus species, commonly called the

two-spot octopus, lives along the coasts of

southern California.² Laboratory studies of

octopus temperament indicate that early

in life, O. bimaculoides is highly mobile

and aggressive, even toward members of

its own species, likely in order to increase

dispersal.³ Mature octopuses follow a

strict hierarchy based on size when they

compete for quality dens; the octopuses

can visually recognize their relative status

compared to other individuals, and avoid

dangerous physical encounters with larger

conspecifics. 4 Though O. bimaculoides is

typically a solitary species, the octopuses

suspend the avoidant behavior associated

with maturity while mating. 5 Such stark

shifts in behavior during mating periods

reflect the organism’s reproductive strategy

as both anisogamous (the eggs is much

larger than the sperm) and semelparous

(the organism dies after a single bout of

reproduction).

Noting these behavioral changes and

their underlying neural mechanisms, Eric

Edsinger and Gül Dölen—researchers

at the Woods Hole Marine Biological

Laboratory and Johns Hopkins University

respectively—began studying the

influence of stimulants on octopus social

behavior. They soaked octopuses in

3,4-Methylenedioxymethamphetamine

(more commonly known as MDMA or

ecstasy) to investigate whether the MDMA

would have the same prosocial effects on

the octopuses as it has on humans. 6 MDMA

changes the way serotonin affects the

brain, and the researchers believed that

similar mechanisms might cause octopuses

to deviate from their typical antisocial

behaviors. The researchers hypothesized

that serotonin mediated pathways are

suppressed during most of the octopus life

cycle, and that they could use MDMA to

activate these mechanisms outside of the

reproductive period.

SLC6A4,

the human

serotonin

transporter gene,

has conserved

orthologs in both

humans and

octopuses.

To test their hypothesis, Edsinger and

Dölen designed a tank-based experiment

for female two-spot octopuses. They built a

special tank with three chambers that the

octopus could move between: a chamber

with a neutral object, an empty middle

chamber, and a chamber with a conspecific

social object in it. The conspecific

social object was a male octopus of the

same species and larger size than the

subject octopus. The object octopus was

constrained so that the subject octopus

could interact with it but it could not

interact back. The researchers measured

the amount of time the subject octopus

spent in each chamber, as well as observed

the quality of behavior in each chamber,

before and after MDMA exposure.

Why, though, should we expect MDMA to

have any effect on octopus behavior at

all? In humans, MDMA is known to have

prosocial effects like feelings of closeness

to others, openness to new ideas, and

increased sensory sensitivity. 7 MDMA

affects G-protein-coupled receptors

and induces spikes in dopamine and

serotonin. 8 MDMA interferes with

receptors involved with transport of

the neurotransmitters into and out of

the cell, thus it consequently promotes

release of dopamine and serotonin while

simultaneously downregulating reuptake.

MDMA prevents serotonin from getting

into cells by acting as a competitive

inhibitor at the serotonin transporter, so

MDMA gets transported into cells instead

of serotonin. MDMA promotes efflux of

serotonin out of cells by exchanging with

serotonin in an amine transporter. 9 The

combined increased release of dopamine

and serotonin and downregulation of

reuptake increases their concentrations in

extracellular space and therefore increases

activity in the brain and promotes social

behavior. Dopamine and serotonin in

particular are significant because they are

the main neurotransmitters associated

with reward and addiction; stimulating the

production of these chemicals in humans

causes a range of prosocial effects, most

notably feelings of euphoria. With these

effects on humans in mind, Edsinger and

Dölen hoped that they could use MDMA

to stimulate serotonin and dopamine

production in octopuses to produce

comparable prosocial effects. In other

words, if the octopuses have similar social

mechanisms to humans, then MDMA would

make the octopuses more friendly during

stages in their lifecycle when they would

normally be avoidant.

14 | CATALYST

octo-high:

in octopus bimaculoids

Edsinger and Dölen’s experimental results

indicate just that. While under the influence

of MDMA, the subject octopuses spent

significantly more time in the social object

chamber. The quality of their interactions

also changed: control octopuses did not

physically interact with the social object,

but subject octopuses engaged in what

the researchers described as “extensive

ventral surface contact, which appeared

to be exploratory rather than aggressive

in nature”. Essentially, the introduction of

MDMA unlocked prosocial behaviors in the

octopuses that they would normally not

express giving their current life cycle stage.

In addition to performing the tank

experiments, the researchers analyzed

several gene groups across animal

genomes to draw evolutionary connections

between species. Specifically, they

examined SLC6A, monoamine transporters,

and the SLC6A4 gene family; these genes

encode transmembrane proteins that

bind amino acids and work to transport

neurotransmitter molecules in and out

of cells. MDMA is known to interfere

with some of the proteins in this group.

Interestingly, the researchers found

that the SLC6A4, the human serotonin

transporter gene, has conserved orthologs

in both humans and octopuses. This

means that humans and octopuses share

By Kelsey Sanders

the same gene from a common ancestor

and that gene serves the same function

in both species, in this case that function

being serotonin transport. This finding

provides evidence that serotonin signaling

as a means of regulating interpersonal

behaviors is evolutionarily conserved in a

diverse range of organisms that abide by

complex social organizations.

In summation, drugs can make an octopus

do some very interesting things. The twospot

octopus is well-known for avoiding

other members of its species, with the

exception of premating aggression and

social behavior during mating. Researchers

sought to manipulate octopus behavior,

specifically inducing prosocial behavior

outside of mating stages, by immersing the

octopuses in MDMA solution. Foremost,

they found that MDMA promoted

exploratory physical contact between

subject octopuses and social objects.

They also analyzed genomic information

and discovered that octopuses and

humans share homologs of a critical gene

responsible for serotonin transport and

MDMA binding. By making headway in drug

delivery protocols for this model species

and by setting the groundwork for future

translational investigation, these results

prove important for biologists and medical

professionals alike.

Works Cited

[1] Boal, J. G. Vie et Milieu 2006, 56.2, 69-80.

[2] Forsythe, J. W.; Hanlon, R.T. Mar. Biol.

1988, 98.3, 369-379.

[3] Sinn, D.L. J. Comp. Psychol. 2001,115.4,

351.

[4] Cigliano, J.A. Animal behaviour 1993,

46.4, 677-684.

[5] Mohanty, S.; Ojanguren, A. F.; Fuiman, A.

L. Mar. Biol. 2014, 161.7, 1521-1530.

[6] Edsinger, E.; Dölen, G. Curr. Biol. 2018,

28, 1-7.

[7] Krystal, J.H. et al. Am. J. Drug Alcohol Ab.

1992, 18.3, 331-341.

[8] Bankson, M.l G.; Cunningham, K.A., JPET

2001, 297.3, 846-852.

[9] Rudnick, G.; Wall, S.C. Proc. Natl. Acad.

Sci. USA 1992, 89.5, 1817-1821.

DESIGN BY Sarah Swackhamer

EDITED BY Laura Jabr

Time Spent

With

Toy

With

Friend

Pre-MDMA

Post-MDMA

CATALYST | 15

IT'S ALL IN YOUR BRAIN

THE NEURAL NETWORK OF CHRONIC PAIN

By Tammita Phongmekhin

A

medical maxim goes: “The extent of

pain one feels is directly proportional

to the severity of the physical injury.”

Through decades of research, this idea

has largely been debunked by the scientific

community. However, much of the general

population still believes in this common

misconception.

This idea of pain being proportional to

the amount of tissue damage ties into

the subject of chronic pain. Chronic pain

is defined as pain that persists for longer

than three months. Those that suffer from

chronic pain conditions often feel a degree

of pain that exceeds the extent of physical

injury, if such an injury even exists. Chronic

pain can make even the most basic tasks

unbearable; additionally, these conditions

can be especially hard to treat, as they often

do not present visible symptoms. As Dr.

Leslie J. Crawford, Vanderbilt University’s

rheumatology research director, states:

“[chronic pain is] perhaps the symptom that

brings more patients into our practices than

any other, but also the symptom most likely

to make us feel helpless as healers.” 1

Chronic pain is an artifact of the brain. Just

as learning and repetition rewire the brain,

prolonged pain can alter the brain’s neural

networks, causing a heightened sensitivity

to pain which further amplify the effects it

has on emotional and cognitive abilities.

As such, chronic pain modifies the central

nervous system, induces mental disorders,

and negatively affects a person’s lifestyle. 1

Therefore, healthcare professionals consider

it to be both a physical disability and a

neurological disease.

A Negative Remolding of the Brain

There are multiple physical symptoms and

alterations that are observed in chronic pain

patients, and they are largely centralized

in the brain and the nervous system of the

body.

One symptom involves a decrease in gray

matter, which results in a decreased ability

to perform tasks involving muscle control,

sensory perceptions, and memory. Patients

may also experience shrinkage of their

prefrontal cortex, leading to difficulties

controlling the brain’s executive functions

like decision-making. Reduced hippocampus

size has also been observed in chronic pain

patients--a physiological change which

causes increased likelihood of developing

anxiety and depression. 2

“

Chronic pain can make

even the most basic

tasks unbearable. These

conditions can be

especially hard to treat, as

they often do not present

visible symptoms.

”

Additionally, studies confirm that chronic

pain patients who undergo these changes

in brain structures have cognitive and

emotional modulation of pain. As patient

conditions worsen and emerge as chronic

pain, brain activity shifts from traditional

pain-related areas of the brain to those

areas associated with emotions. 3 These

findings not only explain why many

chronic pain patients develop anxiety

and depression, but also why those who

experienced periods of high stress prior to

injury are more prone to develop chronic

pain once they are injured.

Heightened Sensitivity

In addition to physical changes in the brain,

prolonged pain affects the state of the

nervous system, resulting in heightened

sensitivity to pain and emotional difficulties.

Central sensitization is the condition in

which the nervous system experiences a

constant state of high reactivity, effectively

lowering the threshold for pain and causing

pain to last even when the initial injury may

have healed. Central sensitization is also

associated with emotional distress since the

nervous system’s high reactivity state causes

a person to be in a state of nervousness.

When patients acquire an injury or

illness, predisposing factors play roles

in determining whether or not they will

develop chronic pain. For example, a

history of stress corresponds to a more

reactive nervous system, thereby making a

16 | CATALYST

person more vulnerable to develop central

sensitization after injury. Furthermore,

antecedent factors such as stress and fear

augment the nervous system’s reactivity,

feeding into the precarious cycle of chronic

pain. 4

Treatments

Unlike acute pain, chronic pain typically does

not have a definite end and the objective

of its treatment often focuses on lifelong

management rather than complete remedy.

However, the nervous system’s ability to

adjust itself over time allows neural changes

caused by persisting pain to be reversed to

an extent through appropriate treatments.

One type of treatment aims at directly

changing the body/brain through medication

and physical therapy, while another type

aims at improving the psychological/

emotional state through counseling. As

chronic pain is physical, psychological, and

neurological, doctors often recommend a

combination of both types of treatments for

effective chronic pain management.

Medication and Physical Therapy

While medication helps reduce pain and

muscle tension, long-term use of opioids can

result in severe side effects such as bleeding

ulcers and liver failure, as well as addiction

and overdose. 5 Thus, a more effective

treatment often consists of a combination

of medication with physical therapy and

counseling.

Physical therapy and regular exercise help

patients regain flexibility, build strength and

endurance, and decrease pain and stiffness.

Moreover, exercise releases feel-good brain

chemicals that improve mood and lower

stress. Research also shows that engaging in

appropriate and frequent physical activity is

usually one the best treatments for chronic

pain. 6

Psychological counseling

Finally, psychological counseling helps

people cope with frustration and

negativity that accompany prolonged pain.

Psychologists design personalized treatment

plans where they teach the patient

relaxation techniques, change the patient’s

perspective on pain, and work with the

patient to change his or her thoughts and

behaviors so that he or she will be able to

better manage the emotional and physical

pain.

Since emotions affect the nervous system,

psychological treatments can change the

way the nervous system responds to pain.

In some cases, psychological counseling has

been shown to be as effective as physical

therapy, medication, and even surgery. 8

Conclusion

Up to 25% of the population experience

chronic pain. In addition, most of these

conditions disproportionately affect

women (up to 70% of patients suffering

from many chronic pain disorders such as

fibromyalgia, irritable bowel syndrome,

and temporomandibular joint disorder are

women) and may take years to diagnose.

Furthermore, chronic pain is not included

in the Social Security Disability List of

Impairments, even though it oftentimes

results in unemployment and long-term

disability. 1

Since chronic pain is an invisible illness,

the general populace and even medical

practitioners tend to empathize less with

and dismiss pain reports from chronic

pain patients. 9 This stigma fosters distrust,

results in the patient feeling ashamed and

misunderstood, and discourages the patient

from seeking professional help. However,

chronic pain is a real disability that will

exacerbate without proper treatment.

Fortunately, there is great progress in

chronic pain research. New treatments are

being developed and many people have

come to realize that chronic pain is an

unseen reality that needs to be addressed.

Works Cited

[1] Crofford, L. J., Trans. Am. Clin. Climatol.

Assoc. 2015, 126, 167-183.

[2] Pain Management and Injury Relief

Medical Center. paininjuryrelief.com/

chronic-pain-brain (accessed Oct. 13, 2018).

[3] Hashmi, J. A. et al., Brain. 2013, 136,

2751–2768.

[4] McAllister, M.J., Institute for Chronic Pain.

instituteforchronicpain.org/understandingchronic-pain/

what-is-chronic-pain/centralsensitization


[5] American Society of Regional Anesthesia

and Pain Medicine. https://www.asra.com/

page/46/

treatment-options-for-chronic-pain

(accessed Oct. 17, 2018)

[6] Feinberg, S. et al. American Chronic Pain

Association. theacpa.org (accessed Oct. 17,

2018)

[7] Healthline. https://www.healthline.com/

health/chronic-pain/chronic-pain-treatmentoptions


[8] American Psychological Association.

https://www.apa.org/helpcenter/painmanagement.pdf


[9] De Ruddere, L.; Craig, K. D., PAIN. 2016,

157, 1607-1610.

DESIGN BY Anna Croyle

EDITED BY Dora Huang

Neural Symptoms

Decrease in gray matter

Leads to decreased ability to perform

tasks involving muscle control, sensory

perceptions, and memory.

Shrinkage of prefrontal cortex

Difficulties controlling the brain’s executive

functions like decision-making.

Reduced hippocampus size

Increased likelihood of developing

anxiety and depression.

CATALYST | 17

Racing towards the

cure for

cancer

By Hannah Boyd

rossing the finish line, Dr. Tour’s

car takes the victory, leading with

Ca margin of about 90 minutes. 1 On

a track of 150 nanometers, six countries

competed in France in 2017 to win the

coveted title. The first of its kind, this race

tested the speed of the smallest cars ever

designed: nanocars. After nearly 20 years of

research, Rice University professor Dr. James

Tour finally created his nanocar, christening

it “the Dipolar Racer”. While winning the

world’s first nanocar race represents an

accomplishment on its own, Tour’s novel

work in nanocar design and synthesis

furthers the discipline of nanoscience

and the manipulation of particles at the

nanoscale.

A working motorized nanocar broke

ground in molecular science, but still

many asked: What next? Inspired by the

nanocar’s molecular motor, Dr. Tour

and his lab group set out to construct

other nanomachines. Nanomachines are

any synthetically designed product that

functions at the nanoscale level. Applying

his synthetic organic research background

to the biological sciences, Dr. Tour, in the

months following the race, began designing

nanomachines which would perforate and

kill target cells. The molecular motors that

once powered the wheels of the tiniest cars

now act as the template for those driving

nanomachines.

The future medicinal application of

nanomachines appears promising. Unlike

widely-used traditional drugs which attack

cells by changing the chemical composition

around them, nanomachines operate

mechanically—leaving behind no chemical

trace. Cells are constantly adapting to their

chemical environments, finding new ways to

survive and building up immunities to each

new drug administered. Where chemical

drugs induce apoptosis (programmed cell

death), perforating cell membranes with

molecular nanomachines induces necrosis

(immediate cell death). Necrosis bypasses

the need for a cell to systematically evaluate

itself before inducing apoptosis. Since cells

cannot adapt to defend against mechanical

damage, nanomachines pave the way for a

class of novel drug designs.

Tour’s nanomachines consist of three

main parts: the fluorophore, rotor, and

the stator. The fluorophore, a particle that

fluoresces when exposed to light, allows

the machines within a sample to be easily

tracked. The rotor, held in place by a stator,

activates and spins when exposed to

ultraviolet light. After the synthesis of the

machines, the first wave of trials tested the

effectiveness and speed of different types

of nanomachines against cell bilayers. To

model targeted cells, researchers used

synthetic bilipid vesicles filled with dye. The

tested nanomachines differed in size and

motor type. After analyzing the data, Tour’s

team found that the smaller machines were

the fastest and most efficient at perforating

the synthetic membranes. 2 The second

wave of trials introduced the nanomachines

to live cells. When exposed to UV light,

the nanomachines induced a substantially

higher rate of necrotic cell death compared

to a control without nanomachines. The

next challenge would be finding a reliable

way to label specific cell to attack. Peptides

can be designed to target specific cellular

recognition sites on different cells, allowing

for the targeted induction of necrosis. After

observing the nanomachines successfully

necrotize live cells, Tour and his group

began studying the effect of adding peptides

to the machine. Matching up with receptors

on the targeted cells, the peptides direct

the machines to the cell that should be

killed. Cell specific death was successfully

observed in live cells when using longer

engineered peptide chains. 2 Being able to

direct the nanomachine to specific markers

on cells allows for huge possibilities within

drug design, especially for the targeting of

cancerous cells.

To test the machine’s effects on live cancer

cell lines, a lab in Durham tested these

molecular machines specific to human

prostate cancer cells in August of 2017.

The nanomachines operated successfully,

inducing cancerous cell-specific necrosis

when activated with ultraviolet light. Detailed

pictures of the process show the membrane

bulge as cytoplasm leaks out of the cells,

dying in as little as one to three minutes. 3

After the publication of these results, many

grew excited towards the potential of a noninvasive

treatment for tumors that resist

chemotherapy.

However, limitations still prevent

nanomachines from clinical implementation.

Tour’s lab group seeks to research methods

that will allow for easier activation of these

machines in vivo. Using ultraviolet light is

disadvantageous when trying to reach cells

within living systems. To offer a solution

to this problem, the group is designing

machines that can be activated by twophoton

absorption or infrared light.4 In

turn, this would allow the activation of

nanomachines past the skin, and aid in the

future directions of using nanotechnology as

a drug treatment for many kinds of cancers.

Work Cited

[1] Davenport, Matt. World’s first nanocar race

crowns champion. Chemical and Engineering

News. 2017, 95, 16-19

[2] Garcia-Lopez, V. et al. Molecular machines open

cell membranes. Nature 548, 567–572 (2017)

[3] Knapton, Sarah. Nanomachines that drill

into cancer cells killing them in just 60 seconds

developed by scientists. Science, 2017.

[4] Williams, Mike. Motorized molecules drill

through cells. Rice News, 2017.

DESIGN BY Abram Qiu

EDITED BY Jenny Wang

Graphic from iStock

18 | CATALYST

The Mitochondria

More Than Just the Powerhouse of the Cell

By Tasneem Mustafa

No matter how much or how little

experience you have with biology,

most of us know one thing:

mitochondria are the powerhouses

of the cell. While this has become a fun

catchphrase to help us remember the

components of a cell, the statement runs

true for a reason: mitochondria are crucial

for the production of adenosine triphosphate

(ATP) – the “energy currency of life” – by

processing sugar from the food that we

consume. However, “powerhouse” is a gross

simplification of the capabilities of this small

organelle, as mitochondria are central to

countless processes such as calcium signaling,

growth signaling, metabolic production, and

activation of multiple cell death pathways.

Here at Rice, mitochondria play a central

role in the research of Dr. Natasha Kirienko,

a professor of Biosciences, as she is

investigating mitochondria’s role in signaling

pathways, which could lead to larger, possibly

life-saving, implications.

Here on campus, Dr. Kirienko runs what

she affectionately refers to as the “worm

lab” as so much of her research has

revolved around the model organism C.

elegans. In fact, C. elegans is a species of

roundworm that is extremely useful in a

laboratory setting, which, according to the

University of Minnesota, “shares many of

the essential biological characteristics that

are central problems of human biology.”

In C. elegans, it is easier to track different

processes such as the mitochondrial damage

pathway illustrated in Figure 1. Healthy

mitochondria are essential to a healthy cell,

as the energy produced through oxidative

phosphorylation of ATP in the mitochondria

fuels the rest of the cell. However, if the

mitochondria are afflicted, the mitochondrial

surveillance pathways will be activated

to attempt salvaging the cell. However,

sometimes the deterioration of mitochondria

continues, preventing the cell from achieving

homeostasis as more functions fail. At this

point, the deteriorated cells will experience

a mitochondrial membrane potential drop

that signifies cell death and makes it a

target for recycling via mitophagy. Recycling

mitochondria may seem like an effective

mechanism to conserve resources, but a

different set of problems can arise. Proteins

can escape from the mitochondria and

end up in the cytosol, which could trigger

apoptosis or cell self-destruction. Dr. Kirienko

further details that the “overactivation of

autophagy will also trigger [a] whole cell

autophagy”, demonstrating how big of an

effect mitochondria can have. Because

of these effects and more, mitochondrial

damage can have dangerous impacts as

this amplification can lead to extensive, and

oftentimes irreversible, cellular level damage

The study of mitochondrial pathways piqued

Dr. Kiriendo’s interest long before she started

her research at Rice. As a graduate student,

she studies mitochondrial mutations in

C. elegans and found a mutant “that was

sensitive to all kinds of stresses...because it

cannot activate [its] ESRE genes”. The Ethanol

and Stress Response Element, or ESRE, that as

Dr. Kirienko explained, can“mitigate damage

from a variety of abiotic stresses”, and though

commonly triggered by ethanol, can also be

triggered by other stressors. So, the mutant

that Dr. Kirienko had found gave the first

hint that there was a connection between

ESRE and mitochondrial mutations. Through

further research, Dr. Kirienko realized that the

ESRE genes can be triggered by mitochondrial

damage due to its connection with “ethanol,

hypoxia, oxidative stress, and pseudomonas,

a common bacteria behind infections, and

iron removal by pseudomonas”. However,

more research needs to be done to further

our understanding of the mechanisms,

especially of the transcription factors,

as they are heavily involved in the in the

signal transduction cascade that starts the

mitochondrial damage.

Interestingly, while Dr. Kirienko’s lab has

always been known as the “worm lab” at

Rice, she is currently shifting her focus from

C. elegans to mammalian cells, which could

be more beneficial for potential cancer

research because they have more similarities

with human cells than C. elegans cells. As

an aid to her future research goals, a fiveyear

grant for nearly $2 million dollars from

the National Institute of General Medical

Sciences to investigate the ESRE pathway and

its mitochondria-repairing mechanisms has

been awarded to Dr. Kirienko. Additionally,

Dr. Kirienko believes that the most effective

way to carry out her research is by continuing

her cross disciplinary research approach. By

integrating different areas of research with

a “biochemical and genetic approach”, Dr.

Kirienko can develop a more comprehensive

picture about mitochondrial repairing

mechanisms. By using bioinformatics, the

Kirienko lab mines large data specifically

available for cancer-related research to

generate a list of genetic mutations and

compare those results with their projects on

C. elegans and mammalian cells. By utilizing

different approaches, Dr. Kirienko’s team can

move forward in their research and into the

world of cancer research.

The mitochondrian plays a crucial role in the

overall health of a cell. We are on the cusp of

learning more about the ESRE pathway and

the role it plays in mitochondrial damage.

If we can find a way to stop or slow down

mitochondrial damage, it will greatly mitigate

the damage as the cell will be more likely to

recover. If we can gain the reins of control

for mitochondria, it might just be the key to

defeating cancer. No wonder mitochondria

are called the powerhouse of the cell.

Repair

Mitochondrial

Surveillance

+ chaperone expression

- translation

Remove

DESIGN BY Krithika Kumar

EDITED BY Yvonne Chien

Healthy

Mitochondria (MT)

Sick

Mitochondria

mitophagy

apoptosis

CATALYST | 19

FLIES

ON THE

PRIZE

Exploring the

interconnectedness

of genetics and behavior

in Drosophila

melanogaster

By Sarah Swackhamer

Though they may seem annoying

or simply insignificant, fruit flies

are much more than a household

pest. In fact, they are model

organisms that guide behavioral scientists

and geneticists in their quest to uncover the

secrets of evolution. These scientists are

asking a big question: what influences how

we live our lives and how we experience the

world around us? In science, as in general,

that isn’t simple to answer. Dr. Julia Saltz,

however, doesn’t shy away from confronting

this conundrum. Instead, she races towards

it with excitement and determination, almost

like a fruit fly who has just spotted its favorite

food: which, incidentally, is exactly what

happens in her lab at Rice University. Using

Drosophila melanogaster and a few sister

species, the Saltz lab analyzes the behavior of

the flies as analogs to human individuals and

communities, diving into our still-unanswered

questions about genetics, behavior, and

evolution and exploring the fundamentals

of life on a small scale with wide-ranging

implications.

Behavioral science is the study of the actions

of animals in their daily lives. For Dr. Saltz,

behavioral science was always a fascinating

subject; genetics, however, didn’t always

interest her. The basics of the field are

widely-known and seemingly-immutable,

she explained: genes produce genotypes,

which contribute to the expression of certain

phenotypes or characteristics. To a young Dr.

Saltz, it seemed that this left little room for

new discovery or creative liberty in the field.

In graduate school, however, she discovered

quantitative genetics: a field working to

analyze intraspecies differences in behavior.

Interestingly, this field focuses on “characters

which are not affected by the action of just a

few major genes”. 1 Dr. Saltz was galvanized

by the opportunity to innovate and explore

she saw in the discipline, and it is at the

crossroads of this field and behavioral science

that her lab now operates.

Just as behavioral science examines the

actions of animals, in psychology, scientists

endeavor to address questions of behavior

in humans; however, they face many

limitations on the extent of research that

can be conducted. For example, a scientist

can’t expose a child to trauma simply to

observe its impacts. Another issue of human

research emerges from each individual’s

ability to uniquely process events, which

throws additional variables into any potential

experiments. Dr. Saltz notes that there are

“a lot of ideas about how individuals might

be exposed to the same thing but perceive it

differently”; in other words, your personality

can actually affect how you experience, and

thus respond to, events in the world around

you.

One surprising recent

discovery, Saltz

remarks, is a

“side preference”:

each fly may only reach

for its food if that

food is, for instance,

on the fly’s left.

Fortunately, using the Drosophila model, Dr.

Saltz is able to dive into some of the same

fundamental questions addressed by human

psychology in a much more controlled

environment. A model species is defined as

one “that has been developed over many

years to be experimentally powerful and

answer particular questions.” 2 In these

respects, Drosophila fits the bill perfectly.

“We have these genotypes that we can

make over and over,” Saltz explains. These

D. melanogaster specimens are “inbred lines

originally derived from a single population

in...North Carolina,” where a project was

developed several years ago to produce a

“community resource of natural variation”.

These clones, “can [be] test[ed]... in all kinds

of situations [without] the same kinds of

ethical and logistical implications” found in

human experiments, Saltz explains. So, these

tiny organisms can actually become vital

players in the quest to uncover fundamental

principles of behavior and evolution.

In particular, Saltz uses the Drosophila model

to help answer one central question: “how

does variation evolve?”. She explains that

this question can be addressed “within

populations and even within individuals” by

analyzing the interactions between organism

and environment. Her lab does this using

several distinct fly populations: Drosophila

melanogaster, primarily, as well as sister

species D. simulans and D. sechellia. But

what does “environment” really mean? It is

a complex idea; put simply, it’s “anything

that’s outside you,” and Saltz primary focuses

on the aspects of environment that directly

affect her flies, such as social and food

environments.

Because of the many elements involved

in evolution and behavior, the Saltz lab is

constantly busy with a variety of projects.

Currently, the primary areas of investigation

include social networks and learning. In her

social network experiment, she is exploring

the factors that play into the development

of social networks and the evolution of

network formation over time. In part, this

involves manipulating a group’s genotypes

to examine the effects on network structure

and evolving flies on different food types to

examine the co-evolution of food preferences

and social behaviors. Additionally, in her

learning experience, she tests her flies’ ability

to process and retain information from

experiences.

20 | CATALYST

In her social network experiment, Saltz and

her lab place groups of 20 flies into Petri

dishes, each containing one of 5 food types.

Each fly is genetically distinct from the

others, but each group of 20 is composed

of the same genotypes. For each trial, the

lab records the flies’ activity on video, then,

using this data, analyzes patterns of social

behavior. “For example,” Saltz explains, “which

genotypes associate with all of their group

mates? Which ones keep to themselves?” This

experiment is helpful to the Saltz lab because

it enables them to “go beyond one-on-one

interactions to understand how each fly fits

into the social structure of the group as a

whole.”

Not every discovery in lab fits perfectly into

the growing picture of evolution that Saltz

and her colleagues across the country are

creating. One surprising recent discovery,

Saltz remarks, is a “side preference”: each

fly may only reach for its food if that food

is, for instance, on the fly’s left. “I’ve sort of

become obsessed with this,” Dr. Saltz admits.

It’s certainly an interesting phenomenon, and

one for which it is difficult to find any rational

basis; “this is not what you would expect

evolution to produce,” she continued. From

the research the Saltz lab has conducted on

side preference, this is not a phenomenon

unique to Drosophila melanogaster and

sister species; it has been observed in

many animals, but researchers generally

don’t know how to handle it and the initial

variables it throws into their studies. From

Dr. Saltz’s perspective, this is an interesting

dilemma; she hopes to further study it in

order to determine whether the observed

side bias is indeed a prevalent pattern, and

if it is, she hopes to move towards a better

understanding of why and how this behavior

has developed.

In her learning project, Saltz examines how

differences in environmental preference are

modified by learning, and how environment is

linked to learning itself. Saltz’s lab conducted

this experiment using D. simulans and D.

sechellia, a sister species that has evolved

to consume specific toxic fruits. In each

trial, a fly is placed into an environment that

contains both normal fly food and food that

has been modified to mimic the toxic fruit

favored by D. sechelia. Noting the amount of

time a fly spends with each food type, the lab

the so-called dichotomy

of nature versus nurture

is really much more of a

grey area

can determine which food is preferred. After

this is established, the flies enter a “training

phase” in which one of the foods in the arena

is spiked with an “aversive bitter compound,”

which should teach the fly that it “is toxic and

should be avoided.” After the flies have been

trained, they are moved to yet another arena;

this one, like the first, contains normal and

modified food without the bitter compound.

Saltz explains that “[b]y comparing th[e flies’]

preference after training to their preference

before training, [the lab] can identify whether

the training… impacted their preference”

and thus whether they learned from the

experience. Saltz’s learning work has been

temporarily thrown off by the discovery of the

side bias, but it should be back on track soon.

Although there is still much to be discovered,

Saltz says, one important advance for

her lab has been the evidence that

“different genotypes experience different

environments” and the so-called dichotomy of

nature versus nurture is really much more of

a grey area. Saltz explains that “nature [can]

produc[e] nurture or guid[e] nurture,” and the

two are often “interacting in complex ways”

to produce the environments that Drosophila

(and we) experience. An example that may

resonate more with us as humans, she

explained, is that of a student who is naturally

athletic. This individual will probably get

access to better coaching and other sportsrelated

resources, while someone without the

same ability, or genetic predisposition, will

probably be left without these opportunities.

It makes sense, but as already discussed,

showing the idea to be true can prove difficult

in human studies. The Saltz Lab’s work,

however, shows that the interconnectedness

of nature and nurture is “real and happens,

and has implications for behavior and…

fitness” of animals.

But where does all of this lead? Dr. Saltz

hopes her research will produce an

understanding of the interactions between

individuals and environments “at multiple

spatial scales… and multiple… evolutionary

time scales” to ultimately generate a theory

that helps to predict variation in behavior.

But the steps towards reaching this goal

aren’t necessarily linear; the lab is working

on so many simultaneous projects that

the process functions more like “putting all

the pieces together” over time. As for the

impacts of her research, beyond elucidating

evolution and behavioral development, Saltz

herself remains open: “that’s the whole goal

of fundamental science, right?” she says;

“there are surprises, and many of them can

be extremely important in ways that we didn’t

predict”.

References

[1] https://www.ncbi.nlm.nih.gov/pmc/

articles/PMC2842708/

[2] https://www.dnalc.org/view/1433-Whatare-Model-Systems-1-.html

DESIGN BY Kaitlyn Xiong

EDITED BY Ananya Subramanian

CATALYST | 21

A New hope for parkinson’s disease:

induced neural

clearance

By luke cantu

Over 10 million people worldwide

live with Parkinson’s disease,

with few treatment options

available. 1 Parkinson’s is a

neurodegenerative disease that is the

result of the slow impairment or complete

loss of dopamine related neurons in the

area of the brain called the substantia

nigra. The substantia nigra is responsible

for motor control and inhibitory action

potentials that regulate signals throughout

the brain. The exact cause of Parkinson’s

disease is unknown; however, there

has been a connection formed between

the disease and the accumulation of a

protein called alpha-synuclein (a-syn) in

the substantia nigra neurons. A-syn is a

protein primarily found in the brain and

plays a role in maintaining a supply of

synaptic vesicles in presynaptic terminals,

meaning it is responsible for maintaining

the neurotransmitter transport that

facilitates the electrical signals between

neurons. This connection between a-syn

and Parkinson’s disease has been found

with other neurodegenerative diseases

and has prompted significant research

into the exact mechanisms responsible for

this connection. However, what precisely

causes a-syn to mutate and become

misfolded remains unknown. Finding

the cause of a-syn aggregation could be

a crucial step in curing Parkinson’s and

other neurodegenerative diseases, as

misfolded a-syn can aggregate and form

insoluble deposits, leading to complete

neuronal impairment or even death. Dr.

Laura Segatori, a professor of chemical and

biomolecular engineering at Rice University,

is pioneering research to answer these

questions. Her lab focuses on developing

methods to control protein levels, which

include engineering nanomaterials to

enhance cell clearance mechanisms, such

as the clearance of aggregated a-syn. She

has successfully reduced a-syn aggregation

by chemically inducing the Hsp70

chaperone system. Yet before this amazing

research can be discussed, a base level of

understanding about the chaperone system

must be established.

The central dogma of biology is that

information flows from DNA then to RNA

and then to protein, and this flow of genetic

information determines the function of

a protein. Often when there is a protein

misfolding,the cause is a mutation in the

genetic code that has resulted in a change

in the sequence of mRNA and subsequently,

affecting the amino acids that construct

the protein. To combat these mutations,

normal mRNA molecules use a family of

proteins called chaperones to help them

properly fold proteins. Chaperones possess

the ability to refold misfolded proteins

back into their proper form. One of the

most well documented small chaperones

is heat shock protein 70, or Hsp70 . Hsp70

posses two domains: an ATP/ADP binding

domain and a protein (substrate) binding

domain. These domains are independently

stable, bind to different substrates or

molecules, and have different properties

that determine the binding substrate and

function of the protein. When bound to

ADP, Hsp70 proteins have a high-affinity

for unfolded proteins and when bound to

ATP, have a low-affinity. Hsp70 proteins

can crowd around an unfolded substrate,

stabilize it, and prevent aggregation until

the unfolded molecule folds properly, at

which time the Hsp70s will lose affinity for

the molecule and diffuse away. An increase

in expression of Hsp70 also leads to a

decrease in cells undergoing apoptosis.

With this background in mind, Dr.

Segatori hypothesizes that “cells with an...

accumulation of aggregated proteins do

not have enough of these chaperones to

deal with these aggregated proteins.” To

investigate this phenomena, Dr. Segatori’s

Pore

Insoluble

aggregate

ATP

ATP

ATP

CIpB/Hsp104

(cross-section)

DnaK/Hsp70

chaperone system

Interaction of

CIpB/Hsp104,

DnaK/Hsp70,

& aggregate

ADP + P 1

Extraction &

threading of

polypeptide

ADP + P 1

Release of

unfolded

polypeptide

Spontaneous or

chaperonemediated

folding

22 | CATALYST

Normal

Parkinson’s Diseas e

Movement

Disorders

Cell Death

Dopaminer gic Neuron

Substantia

Nigra

A-syn Monomers

A-syn

Oligomers

A-syn

Aggregate

approach involves nanoparticles with

a surface layer that contains different

chemical and physical properties that

allows them to interact with different parts

of the cell in specific ways. For example,

nanoparticles in drug delivery that are

engineered for membrane passage allow

for the drug to be transported to the place

of action that the drug would not reach

on its own. Thus, the drug’s influence on

targeted tissues can be optimized and the

undesirable side effects on vital organs can

be minimized along with protecting the

drug from rapid degradation or clearance. 2

This same concept is applied with Dr.

Segatori’s work; she designs nanoparticles

that have specific chemical properties such

as polarity or solubility that allow for them

to pass cellular membranes and specifically

bind to different parts of DNA. This in turn

induces changes with the chaperone system

without inadvertently affecting other parts

of the cell. Another unique approach by

Dr. Segatori is the use of colocalization,

which employs fluorescence microscopy.

Fluorescence microscopy is when specific

proteins or molecules in a cell are stained

or made to have a specific fluorescence

through genetic alteration and are then

viewed through a fluorescent microscope.

Colocalization is simply observing if the

different fluorescent “targets” are located in

the same area of the cell or very near to one

another. This allows for the quantification

of aggregated proteins in a cell before and

after an induction of Hsp70 to determine if

there is a relationship between Hsp70 and

aggregated protein levels.

The purpose of Dr. Segatori’s research is

to demonstrate a proof of principle study

that would then allow for the further

investigation of utilizing nanoparticles to

upregulate Hsp70. In one study, Dr. Segatori

investigated the effects of carbenoxolone, a

chemical compound previously reported to

upregulate Hsp70, in human neuroglioma

cells (a model for substantia nigra neurons)

overexpressing a-syn. 3 By introducing

carbenoxolone into a cell and analyzing the

proteins present with colocalization, it was

found that carbenoxolone increased the

presence of Hsp70 by 52% and decreased

the probability of protein aggregation

from 67% to 37.2%.3 By establishing a

relationship between Hsp70 levels and

protein aggregation, researchers can

develop ways to induce changes in cell

systems to clear aggregated proteins. With

these findings, Dr. Segatori is currently

working on a new way of tackling the

problem of protein aggregation by

designing a nanoparticle that could cause

a system level change or, “essentially

reprogram the cell to respond to a stimulus

associated with a phenotypic trait of a

disease.” Dr. Segatori is searching for a

way to design a genetic circuit to interface

with these pathways and modulate the

response of cell in response to a stimulus.

Such stimulus could be the aggregation of

protein which, through the genetic circuit,

could then be linked to the ability of the cell

to induce the chaperone system to respond

to the stimulus. Then once the stress is

removed the chaperone system would

subside, hence resulting in a feedback loop.

However, there are still challenges, such

as ensuring nanoparticle passage across

the highly selective blood brain barrier and

designing a nanoparticle with a specific

genetic alterations to enact system wide

change.

The application of Dr. Segatori’s work is

limitless, but she is currently investigating

how the use of her nanoparticles could

activate clearance activity within neurons in

an attempt to prevent neurodegenerative

diseases. Dr. Segatori relates her research

and its possible applications to a two

sided coin: “This is a side of the same

coin, on one hand you are thinking of

developing a treatment for a disease, a

treatment for aggregated proteins that is

not just Parkinson’s but also misfolding

protein diseases. On the other side there is

understanding how to design nanoparticles

that will interface with biological systems.”

This dichotomy is the future of her work

and all work in biological nanoparticles.

Works Cited

[1] P. (2019, March 28). Statistics. Retrieved

from https://www.parkinson.org/

Understanding-Parkinsons/Statistics

[2] Uddin, M. D. (2019). Nanoparticles

as Nanopharmaceuticals: Smart Drug

Delivery Systems. Nanoparticulate

Drug Delivery Systems, 85-120.

doi:10.1201/9781351137263-3

[3] Kiri Kilpatrick, Jose Andres Novoa,

Tommy Hancock, Christopher J. Guerriero,

Peter Wipf, Jeffrey L. Brodsky, and Laura

Segatori ACS Chemical Biology 2013 8 (7),

1460-1468

[4] Ruipérez, V., Darios, F., & Davletov,

B. (2010). Alpha-synuclein, lipids and

Parkinson’s disease. Progress in Lipid

Research, 49(4), 420-428. doi:10.1016/j.

plipres.2010.05.004

DESIGN BY Luke Cantu

EDITED BY Minjung Kim

CATALYST | 23

UNCOVERING THE MECHANISM OF PROTEIN FOLDING

AND OTHER COMPLEX SYSTEMS

by NamTip Phongmekin

I

magine being told to fold a paper crane.

There is no representation of what the

end product should look like, and you

have a time limit to transform a sheet

of paper into an intricate piece of art. This

analogy demonstrates the two major issues

of the “protein folding problem,” which

describes the complexity of (1) how proteins

fold into three-dimensional structures

from their linear polypeptide chains, and

(2) how folding pathway(s) allow proteins

to fold so quickly [5,6]. Because proteins

are indispensable to numerous biological

processes, for decades, this problem has

puzzled and intrigued an eclectic group of

biochemists, structural biologists, chemists,

and physicists.

One such researcher is Dr. Peter G. Wolynes,

a D.R. Bullard-Welch Foundation Professor

of Science who has several positions in

the departments of Chemistry, Physics

and Astronomy, BioSciences and Materials

Science and Engineering at Rice University.

Among his long list of accolades, he is a

member of the National Academy of Sciences

and the American Academy of Arts and

Sciences. Dr. Wolynes was initially fascinated

by chemical reactions, but eventually started

to seek out new problems. He asked himself

“what are the most complicated systems

that have chemical change in them?” This

question lead him to delve into issues

with biological systems at the interface of

chemistry and biology.

Protein folding is an intriguing process that

involves various chemical and biological

change from many interactions ranging

from those of the peptide chain backbones

and amino acid side chains to interactions

between different protein subunits. Dr.

Wolynes’ research on protein folding both

describes folding kinetics and predicts

three dimensional native structures, or the

folded form of a protein. A central theme of

his work has been studying protein folding

using the energy landscape theory, which

represents the energy state of different

folding conformations in a form analogous to

a topological map [1,5,6].

Wolynes and his colleagues describe

the energy landscape of a protein as a

“rugged funnel,” in which the surfaces

of the landscape represents a statistical

description of the potential energies of

the protein [7]. The width of the funnel

corresponds to the conformational entropy

while the depth represents the total change

in Gibbs energy between the unfolded

and the folded, or native, state [x]. The

energy state of folded state corresponds to

the bottom of the funnel while the top of

the funnel represents the unfolded state

[xx]. Moreover, the “rugged funnel” model

WOLYNES LAB HAS BEEN

USING COMPUTATIONAL

TOOLS TO ANALYZE

PROTEINS INVOLVED

IN THE ASSEMBLY OF

SYNAPSES AND NEURONS

IN MEMORY FORMATION.

describes that proteins can take on many

paths, involving different intermediate

conformations to reach its final native state

of a corresponding, favorable energy level

at the bottom of the funnel [1]. This process

is represented by a “rugged” landscape

containing local minima corresponding to

different semi-stable intermediates [7]. The

rate of folding is determined the ruggedness

of the landscape; the more local minima

the landscape contains, the more likely the

protein may be trapped in its intermediate

forms, decreasing the folding rate [x]. The

smoother the surface, the faster a protein

folds [6].

The protein folding process is spontaneous,

driven by hydrophobic interactions and

intramolecular forces such as hydrogen

bonding and van der Waals interactions

[xxx]. In addition, while the conformational

entropy of the protein decreases as it moves

down the funnel (the width of the funnel

becomes narrower closer to the bottom of

the funnel), the entropy of the surrounding

water actually increases as the protein folds

due to the hydrophobic effect. These effects

drive protein to ultimately fold into its native

state.

In order to solve protein structures and gain

insight on their folding mechanisms, Wolynes

lab has utilized computer simulations of

proteins. One technique of modeling they

use is template-free, or ab initio structure

prediction, which involves modeling protein

tertiary structure using atomic models from

molecular physics rather than experimentally

resolved structures and homology models,

which may be limited by template availability

[1]. Currently, some of his projects

involve models for protein misfolding and

aggregation for multiple neurodegenerative

disorders, including Alzheimer’s, Parkinson’s,

and prion diseases [5,6].

Dr. Wolynes describes working on the

“memory problem,” or the problem of

setting up a fairly large structure in the

cells to form memories. Wolynes lab has

been using computational tools to analyze

proteins involved in the assembly of

synapses and neurons in memory formation.

The functional role of these proteins have

implications in neurodegenerative disorders.

Long-term memory formation involves

localized synaptic protein synthesis [13]. This

requires a stable, translational regulatory

system at synapse, however, most proteins

have a relatively short half-lives in eukaryotic

cells, and are thus not ideal for maintaining

protein synthesis in the time scales required

for long-term memory formation [13]. An

unusually stable protein, however, was

previously identified experimentally as a

potential player in this synaptic protein

synthesis process [12].Specifically, the

24 | CATALYST

protein folding funnel

energy

graphic does not represent actual protein folding steps

protein contains a Q-rich domain believed

to allow the formation of stable β-oligomeric

forms resembling those of prions molecules

[13].

Wolynes lab builds upon those

experimental findings by providing a

computational description of the kinetic

and thermodynamic stability of the folded

protein structure. They have proposed that

the interactions with synaptical cytoskeletal

elements may mechanically catalyze the

formation of the stable, fibrous prion form

of the protein. This in turns creates a positive

feedback loop that localizes fiber formation

at active synapses for forming longterm

memory [13]. Moreover, studies on

neurodegenerative disorders have identified

certain oligomeric forms that are cytotoxic.

Work in Wolynes lab has suggested that the

cytoskeletal components may be the key

to this transition from the functional to the

pathogenic fiber forms. These findings have

led to a new proposal for targeting domains

that bind to cytoskeletal components rather

than Q-rich domains for treatment of

neurodegenerative diseases[13]. Dr. Wolynes

expresses excitement from the work, stating

that “the assembly of the parts of the cell are

really quite different from the way people

[previously] thought.”

Although a major part of Wolynes lab

has focused on protein folding, research

in his group can be broadly defined as

the chemistry and physics of many-body

systems, or the study of properties and

interactions of complex systems on the

molecular level. In addition to protein

folding, one major area of research in the

Wolynes group is trying to describe the

folding and structure of chromosomes,

which are crucial to gene regulation, DNA

replication, and the cell cycle [8]. However,

predicting the folding of chromosomes

is challenging because it involves many

different players, such as protein complexes

and cytoskeletal elements [9]. Despite

progress, Dr. Wolynes describes his lab has

faced several challenges in elucidating the

structure of chromosomes. He explains, “It’s

an odd [problem] because... we can predict

the structure [of chromosomes] but we’re

not exactly sure how to build the bridge

from the structures that we can predict back

to the way that all the mechanisms work.”

Like folding an origami, the problems

of many-body biological systems can a

complicated. However, the protein and

chromosomal folding processes are crucial

for various biological systems in healthy and

disease states. In protein folding, the energy

landscape model can we used to describe

its pathways to attain the native state.

Analyses on the stability of proteins involved

in synaptic formation has shed new light

on the formation of long-term memories.

Chromosomal folding involves more players,

but analysis on their energetics has provided

new insights regarding its mechanism.

Wolynes lab works on diverse topics, and

utilizing expertise from computation,

chemistry, physics, and biology, they have

discovered and will continue to uncover

the mechanisms of many more complex

systems.

WORKS CITED

[1] https://onlinelibrary.wiley.com/doi/

abs/10.1002/ijch.201300145

[2]https://www.jstor.org/stable/41703986?pq-origsite=summon&seq=1#metadata_info_tab_contents

[3] P. G. Wolynes in Protein folds: A Distanc[9]https://search-proquest-com.ezproxy.

es Based Approach (Eds.: H Bohr, S. Brunak),

CRC, Boca Raton. 1996, pp. 3–17.

[4] P. G. Wolynes, W. A. Eaton, A. R. Fersht,

Proc. Natl. Acad. Sci. U.S.A. 2012, 109,

17770–17771.excelsior%3Abdf36fd6e0c-

539ce246c2665d15a608b

[5] https://www.ncbi.nlm.nih.gov/

pubmed/30304819

[6]https://www.ncbi.nlm.nih.gov/

pubmed/30250260

[x]http://science.sciencemag.org/content/267/5204/1619.long

[xx]http://eds.a.ebscohost.com.ezproxy.rice.

edu/eds/pdfviewer/pdfviewer?vid=1&sid=fd-

486bec-db4a-4d58-8d8d-d44189a00fbd%-

40sessionmgr4007

[xxx]Pratt C, Cornely K (2004). “Thermodynamics”.

Essential Biochemistry. Wiley. ISBN

978-0-471-39387-0. Retrieved 2016-11-26.

[7]http://eds.a.ebscohost.com.

ezproxy.rice.edu/eds/pdfview-

er/pdfviewer?vid=1&sid=0ae-

8c8c4-8ef1-4fc7-9651-c74e4c7361cc%40sdc-v-sessmgr04

[8]https://www-jstor-org.ezproxy.rice.edu/

stable/pdf/26462741.pdf?refreqid=excelsior%3Abdf36fd6e0c539ce246c2665d15a608b

[9]https://search-proquest-com.ezproxy.rice.

edu/docview/274166830?accountid=7064

[10]http://www.pnas.org/content/113/18/5006

[11]https://www.ncbi.nlm.nih.gov/pubmed/6504122?dopt=Abstract

[12]https://www.ncbi.nlm.nih.gov/

pubmed/22583753

[13]https://www.pnas.org/content/113/18/5006

DESIGN BY Priscilla Li

EDITED BY Adelle Jia

CATALYST | 25

DOWN

TO THE NEURONS:

MICRO-METHODS OF MEASURING THE BRAIN

BY ADELLE JIA

H

undreds of years ago, scientists mapped

out regions of the brain by feeling different

bumps on the scalp in the practice of

phrenology. Thankfully, they have developed

much better ways to study the structure of

the most complex organ in the body. For

clinical measurements, physicians rely on

functional magnetic resonance imaging

(fMRI) or EEGs, the “swimming caps” with

hairlike wires flowing from nodes on the

scalp. However, these non-invasive methods

capture the big picture rather than look at

individual groups of neurons: fFMRIs show

blood flow in relatively large regions of the

brain, while EEGs capture the electrical

activity of millions of neurons at once [1]. To

pinpoint neural mechanisms of specific cognitive

functions such as learning, movement,

or perception, researchers implant devices

directly into the brains of animals. Dr. Jacob

T Robinson, a professor at the Bioengineering

and Electrical and Chemical departments

at Rice, is innovating new technologies

that help researchers study the brain at

this microscopic level. These technologies

include microfluidic devices, which enhance

the clarity of neural activity recordings, and

the world’s smallest lensless imaging system,

Robinson's laB has developed

a technology that uses

microfluidic channels

to eject flexible carbon

nanotube fiber (CNTf)

electrodes, which are about

ten times thinner than a

strand of hair.

which computationally constructs an image

from sensor data.

To measure the electrical activity of the

brain, scientists can use microelectrodes

inserted into the neural tissue. A basic

microelectrode consists of a glass

micropipette (10-100 microns in diameter)

that penetrates a neuron’s membrane. These

microelectrodes can accurately measure

the activity of neurons by detecting the

differences in electric potential between the

inside and outside of the cell [2]. However,

it is extremely hard to measure a good

sample of neurons with just one probe.

Imagine using this pipette to measure the

electrical activity of one square millimeter of

brain tissue, which contains approximately

one million neurons! To measure multiple

neurons at once, an optimized electrode

array can detect neuronal activity at tens of

thousands of recording sites.

When the electrode array is being implanted,

the brain doesn’t recognize the electrode

and tries to protect itself by encapsulating

the electrode in a layer of fibrotic tissue

and glial cells. “The electrode has difficulty

reading signals, and as a result, the quality

of the recordings tends to degrade over

time due to the inflammatory response.

The bottom line is that the inflammatory

effects tend to limit the longevity of the

electrodes until they tend to fail over time,”

Robinson says. To reduce an inflammatory

response and provide accurate recordings,

microelectrodes themselves have become

ultra flexible. However, the process of

injecting these flexible electrodes presents

some challenges. First, electrodes can

buckle because of their flexibility, which

prevents them from penetrating the brain.

Different techniques can temporarily provide

support to the electrode as it is inserted,

such applying a stiffening agent or attaching

a probe, but these methods temporarily

enlarge the size of the electrode, which is a

major factor in the cause of inflammation.

To address these challenges, Robinson’s

lab has developed a new method that uses

fluids to insert electrodes instead of syringes.

Fluids’ unique properties have founded

incredible natural phenomena and essential

technological applications. Robinson’s

lab has developed a technology that uses

microfluidic channels to eject flexible carbon

nanotube fiber (CNTf) electrodes, which are

about ten times thinner than a strand of hair.

Inside these channels,

the electrode travels

in viscous fluid, which

prevents both buckling

and inflammation.

These channels are built on a chip, which is

formed by using a mold that is casted with

a pattern of channels on it. “When we peel

the rubber up, it has embedded within it

the channels we’ve designed. It’s sort of like

making a jello mold.”

Inside these channels, the electrode travels

in viscous fluid, which prevents both buckling

and inflammation. This chip rests on the

surface of the brain and extrudes the

electrodes and some fluid into the brain,

leaving behind soft and flexible “cooked

spaghetti noodles.” By varying the velocity of

the fluid flow, they can control how fast and

thus how far the electrode goes. First, they

tested the microfluidic device on the Hydra

Littoralis species, which are challengingly

soft, and were able to detect the action

potentials associated with different

movements[3]. Next, they were able to drive

these electrodes several millimeters deep

first into brain slices of mice, and then cortex

of several rat brains.[3]

One major challenge of implementing this

microfluidic device was preventing the

26 | CATALYST

THE ROBINSON LAB’S MICROFLUIDIC DEVICE

uses fluids to inject electrodes instead of syringes.

FLATSCOPE, a lensless imaging system small enough to

be implanted in the brain and minimize tissue damage.

excess fluid from going into the brain and

causing intracranial damage, which is typical

of syringe injection. To solve this, they built

the chip so that it had vent channels that

prevent 93% of the fluid from entering the

brain. Just at the edge of the chip, the fluid

gets sucked out at a 90 degree angle on both

sides while the electrode continues to go

straight into the brain. Since this redirection

of fluid exerts balanced horizontal forces, the

electrode doesn’t get vertically sucked back

into the chip.

Robinson envisions that this technique “can

be employed for a variety of flexible neural

probes and may become the preferred

delivery technology.’ [3] Although this new

technique presents major steps in limiting

an inflammatory response, Robinson’s lab is

working on several future steps. While it is

hard to gauge the accuracy of implantation,

the goal is to inject lots of electrodes to

increase the probability that some of them

land in the desired area. Additionally, they

are working on looking for different animals

to test this device on.

In addition to microfluidic channels,

Robinson’s lab has also developed lensless

imaging systems small enough to be

implanted in the brain and minimize

tissue damage. Lenses focus light so that

it forms an image, which is picked up by

a sensor. Although lenses give an exact

one-to-one mapping of an image, they

have several physical limitations that make

them difficult to use as they get smaller

and smaller; resolution, light collection

efficiency, and field of view (FOV) become

severely compromised. Lens material

needed for wavelengths outside of the

visible range are expensive and harder to

fabricate. Robinson’s lab uses computational

algorithms to reconstruct an image from

data gathered from sensors. Benefits from

lensless camera include more inexpensive

and high quality production, thin size, shape

flexibility, and the ability to pick up many

ranges of wavelengths and create 3D images.

An interesting application of lensless imaging

Robinson’s lab has recently been working

on is FlatCam. The compact size and lower

cost makes FlatCam a potential candidate

for imaging applications outside of the

lab, such as face detection, surveillance,

and household appliances. Robinson’s lab

recently conducted a study to test if the

resolution of lensless imaging systems was

suitable enough for face detection. First,

they created the FlatCam Face Dataset

(FCFD) with 24,112 images of 88 faces with

different angles, lighting, expressions, etc.

to test the face detection system. As for the

computational method used to analyze the

faces, they chose an accurate method (called

Faster R-CNN), which proposes and classifies

regions that may contain certain “objects.”

Then, they used pre-existing face datasets

to train these deep-learning techniques

before testing them on the FCFD. While

lensless imaging is not yet up to par with lens

imaging, the performance is suitable enough

to detect relatively forward-facing, well-lit

faces. Thus, minimizing the quality difference

between lensless and lens imaging is another

goal researchers plan to tackle.

As for application of lensless imaging to

neuroimaging techniques, Robinson’s lab

has also been developing FlatScope, the

first lensless imaging system specifically for

fluorescence imaging of biological samples.

Genetic techniques allow expression of

proteins that convert electrical/calcium

activity into fluorescence. These fluorescent

proteins can be excited by light of one

wavelength and emit light of a different

wavelength. However, fluorescence is usually

difficult to capture without lenses because it

is an incoherent source- a light source with

photons of different frequencies and waves

WHEN THEY TESTED THE

FLATSCOPE, THEY FOUND THAT

IT COULD PRODUCE HIGH-

RESOLUTION IMAGES WITH A

FOV 10X GREATER THAN THE FOV

OF A LENS MICROSCOPE WITH A

SIMILAR SENSOR.

that are not in phase. This is opposite of

coherent sources such as laser light, which

are easy for sensors to measure because of

their uniform waves. To “sort out” the light

from an incoherent source, the FlatScope

uses different types of masks fitted to the

sensor. The mask could be a 2-D array of

pinholes fitted to the sensor that gathers

information on the angle and intensity of

the light. Instead of an array of pinholes,

this mask could also be a phase mask, which

diffuses the light and causes interference

patterns, from which the algorithms can

discern direction of light.

When they tested the FlatScope, they found

that it could produce high-resolution images

with a field of vision (FOV) 10 times greater

than the FOV of a lens microscope with

a similar sensor.[5] Additionally, it could

reconstruct 3D volume 40,000x faster than

a confocal microscope, which is a lensbased

fluorescence imaging system. All of

the data gathered by FlatScope is analyzed

on a separate computer, which can take

between 100 ms to a couple of seconds to

computationally derive an image pattern

from the interference data.

Although Robinson is working on these two

techniques of measuring or recording brain

activity separately, ideally these methods will

used in combination with each other. “One

day, we do envision these things merging,

multiple ways to record and stimulate activity

becoming one system of distributed sensors

and actuators in the nervous system.”

WORKS CITED

[1] Neuroimaging: Visualizing Brain Structure

and Function. Neuroethics http://ccnmtl.

columbia.edu/projects/neuroethics/

module1/foundationtext/index.html

(accessed Dec. 16, 2018.)

[2]Robinson, J. et al. Front. Neur. Circuits.

2013, 7, 1-7.

[3] Robinson, J. et al. Nano. Letters. 2018, 18,

326-335

[4]J. Tan, et al. IEEE Trans. Comp. Imag. 2018

[5] Robinson, et al. Sci Adv. 2017, 3

Photos courtesy of the Robinson Lab

DESIGN BY

EDITED BY

Evelyn Syau

Preetham Bachina

CATALYST | 27

M

A

gnetic

Cell Manipulation

By Amna Ibrahim

Magnetic resonance imaging (MRI)

technology and stem cell therapies

are two prevalent widely known and

researched medical techniques that find

their connection through gadonanotubes,

which can be applied to both methods.

Magnetic resonance imaging is a medical

technique that uses magnetism, radio

waves, and computers to capture internal

images of a patient’s body. MRI contrast

agents are used to enhance visibility of

internal workings of the body, the strongest

ones being gadonanotubes. Stem cells are

undifferentiated cells that can develop into

many different types of specialized cells in

the human body. For example, stem cells can

be intentionally relocated into heart tissue so

that they can differentiate into heart muscle

cells and help regenerate damaged tissue.

Naturally, cells are not very magnetic, so

they need to be manipulated in order to be

able to move them from place to place in the

body.

Dr. Wilson has been a professor of Chemistry

at Rice University for around 45 years,

his research specializing in nanomaterial

synthesis for application in diagnostic

and therapeutic medicine spectroscopy &

imaging, as well as nanomaterial synthesis.

His research on magnetic cell manipulation

began in 2005, and intertwines chemistry

research with collaboration at the Texas

Medical Center.

Dr. Wilson’s research is centralized around

gadonanotubes, which are small pieces of

carbon nanotubes that are packed with

many superparamagnetic gadolinium ions.

As a result of their strong magnetism,

gadonanotubes are accepted as the single

most powerful and capable magnetic

resonance imaging agent material currently

known. Dr. Wilson embarked on research

using gadonanotubes in 2005, after

discovering what they were.

Initially, Dr. Wilson and his research team

were studying carbon nanotubes and were

28 | CATALYST

attempting to figure out how to manipulate

carbon nanotubes to make them small and

discrete enough to “clear the body filtering

mechanisms” of the liver and the kidneys,

and able to be excreted after fulfilling their

purpose. The research team had always

worked in the area of developing MRI

contrast agents, and so one day they decided

to take the superparamagnetic gadolinium

ions from that area of foregoing research

and combine it with their new research by

mixing the ultra-short carbon nanotubes

with the gadolinium ions. By a “sort of

serendipity,” as Dr. Wilson says, the ultrashort

tubes and the gadolinium ions had a

mutual affinity for each other and stuck to

each other to form the gadonanotubes.

Dr. Wilson and his group collaborated

“external magnetic fields

were shown to indeed keep

stem cells in place much

longer than they would have

naturally”

with research scientists at the Texas Heart

Institute who were focused on studying

the application of stem cell therapies to

repair cardiac muscle. Together, these two

research teams studied the injection of

gadonanotubes into living tissue to discover

whether this injection would allow the tissue

to be able to be moved around externally

by a magnetic field, which is a discovery that

would open up loads of clinical applications.

When stem cells are injected into a certain

area, they tend to migrate around before

they develop into specialized cells, and so

the gadonanotubes were used to retain

stem cells in the areas where they were

placed, thus allowing them differentiate

precisely at the injection site in the precise

location where they were injected. This

discovery is very beneficial when applied to

patients who have suffered heart attacks

who have damaged and deteriorated heart

tissue – through magnetic cell manipulation,

the stem cells are able to stay in place long

enough to differentiate into healthy, new

heart muscle tissue at the site of a heart

attack.

In addition to their magnetism being of great

use in stem cell therapies, gadonanotubes

are also incredibly valuable by way of their

MRI contrast abilities. Since gadonanotubes

are the most powerful MRI contrast agent

known, they can be externally imaged by MRI

to ensure that the stem cells stay in place at

the location that they are injected. Moreover,

image given by the MRI can be quantitated

in order to determine the concentration

of stem cells/gadonanotubes at the site of

injection.

The significance of the work of Dr. Wilson

and his team, as well as the researchers at

the Texas Heart Institute, was that external

magnetic fields were shown to indeed keep

stem cells in place much longer than they

would have naturally without any form of

magnetic manipulation. Therefore, they were

able to develop into healthy heart muscle

tissue and repair damaged tissue at the

location they were injected in.

The ultimate goal of this research and

its applications is for the gadonanotube

contrast agents to be useful and biocompatible

enough to be used clinically in

order to tangibly help people. However, to

get this research out into the clinic is a very

lengthy process that can take up to a couple

decades, and so this goal is a long-term one,

but instrumentally beneficial nonetheless.

Design by Anna Croyle

Edited by Andrew Mu

Images adapted from Vecteezy

DO YOU HEAR

WHAT I HEAR?

Hair Cell

Regeneration

in the Cochlea

BY MAIA HELTERBRAND

Even when you’re asleep, your ear

never stops hearing or processing

sound. However, once your hair

cells - cells that play a key role in the

auditory system - are damaged, they are

unable to be regenerated. These hair cells

are organized and specialized with inner

hair cells detecting sound and outer hair

cells adjusting the intensity of that sound.

Furthermore, these hair cells detect specific

range of frequencies. Oftentimes hair cells

in the lower part of the cochlea detect highpitched

sounds, while those in the upper

part of the cochlea detect low-pitched

sounds. However, when non-mammalian

hair cells are damaged due to loud noises,

infections, or the natural aging process, can

regenerate they are able to be regenerated.

However, this is not the case for mature

mammalian cochlea. [Put her specific

research question here]

More specifically, in order to hear, the

outer ear funnels sound waves from the

environment towards the eardrum causing

it to vibrate. These vibrations then travel

through a series of bones in the middle

ear which amplifies and sends the sound

towards the cochlea. The snail-shaped

cochlea is filled with fluid that begins to

move in a wave-like manner once the

sound waves are received. This motion then

stimulates the series of cells known as hair

cells. As the hair cells move, the microscopic

hair-like projections situated on top of the

hair cells, known as stereocilia, contact

the overlying membrane. 1 As this contact

occurs, the ion channels on the tip of the

stereocilia tilt to one side, causing ions to

rush in and generating an electrical signal.

This electrical signal is then carried to the

brain via the auditory nerve where it is

processed. 2

when non-mammalian

hair cells are

damaged due to loud

noises, infections,

or the natural

aging process,

they are able to

be regenerated.

However, this is not

the case for mature

mammalian cochlea.

Dr. Melissa McGovern, who is a post-doc

at Baylor College of Medicine, and her

colleagues are currently trying to induce

regeneration of these hair cells in the

cochlea of mature mice. Unlike the mature

mouse cochlea, if neonatal mouse hair

cells are damaged, the surrounding cells,

known as the supporting cells, are able

to spontaneously regenerate into hair

cells similar to the way hair cells in nonmammalian

species regenerate. However,

this ability readily declines as the cochlea

matures and becomes functional, with hair

cells being unable to regenerate after about

two weeks of age.

Therefore, Dr. McGovern and her colleagues

are “trying to find what cocktail of genes

we can express within the supporting cells

to turn them into hair cells” in the mature

mouse cochlea. By comparing marks such

as the number of genes expressed in these

induced(?) hair cells to the genes expressed

in supporting cells and actual hair cells,

Dr. McGovern and her colleagues are able

to see “how close to an actual hair cell”

they are. Although the conversion of a

supporting cell into a hair cell is their main

priority, tackling issues such as the location

and orientation of the hair cell are other key

concerns as they are determinants in the

function and specialization of hair cells.

Understanding the process of hair cell

regeneration and the factors that contribute

to regeneration in mature mammalian

cochlea can help with the process of

developing therapies to restore hearing in

individuals with damaged or lost hair cells.

WORKS CITED

https://www.nidcd.nih.gov/health/how-dowe-hear

https://www.nidcd.nih.gov/news/2009/

its-not-just-about-hair-cells-new-researchshows-tectorial-membrane-plays-moreactive

DESIGN BY Juliana Wang

EDITED BY Sarah Swackhamer

CATALYST | 29

THE

By Christine Tang

HIPPOCAMPUS

HIPPOCAMPUS

Let’s Make Some Memories

An experimental procedure left Henry

Molaison, commonly known as

the famous “patient H.M.,” unable

to form new memories. He had a

lobectomy in 1953 that removed several

deep parts of his brain, including the

hippocampus. 1-2 The hippocampus (HC)

of the brain is commonly known as the

center of learning and memory, but its

processes in storing memory have not

been fully elucidated. I had the pleasure of

working in the Neuroscience department

at UT Southwestern under Dr. Lenora

Volk, who focuses her research on the

HC and the brain’s processes in balancing

dynamic learning and persistent memory.

She is currently working on three main

projects, each related to brain function or

memory consolidation.

Learning can be separated into two major

processes: encoding and consolidation.

Dr. Volk’s first project is focused on

understanding the mechanisms of the

latter and its dependence on sleep.

Dr. Volk utilizes a phenomenon called

hippocampal replay to analyze and

compare the neural firing of animals when

awake and when asleep. Hippocampal

replay was first discovered in 1989

when Dr. Constantine Pavlides from

The Rockefeller University in New York

analyzed place cells, which record the

particular location that an organism is

in, and their effect on the brain’s spatial

tuning. 3 Spatial tuning occurs when a cell

encodes information about an associated

location in the environment. Pavlides

and other researchers performed in vivo

recordings of awake, actively moving

animals, and observed that cells fire in

spatially restricted locations and not

in other parts of the environment.3 By

recording and analyzing cell firing data,

researchers observed that the conscious

neural firing pattern is replayed during

sleep. Therefore, hippocampal replay was

proposed to be “a mechanism by which

the brain consolidates memory during

sleep” (Volk).

Although hippocampal replay is a core

component in theories of sleep models

and memory consolidation, it is largely

untested on neuronal changes because

hippocampal replay events are very short.

This makes neural firing and labeling

extremely hard to record. Dr. Volk is

collaborating with multiple researchers,

one of whom is her husband, Dr. Brad

Pfeiffer, to use a method that circumvents

this problem. When a neuron fires an

action potential, an electrical impulse

that travels down a neuron and sends

signals to the next neuron, intracellular

calcium rises. Dr. Volk takes advantage

of this phenomenon by using a reagent

in neurons that glows green when light

is shined and permanently turns red if a

lot of calcium is present. Because light is

extremely fast, she can shine a light for a

couple hundred milliseconds and see the

active-only neurons turn red. She utilizes

this technique to observe hippocampal

replays in sleep and labels active neurons

to analyze their synaptic properties

and test their long-held hypothesis that

“hippocampal replay events are actually

causing changes in the cells and the HC

and perhaps in the cortex that might be

leading to memory consolidation.”

KIBRA’s genetic

mutations and

binding partners

are associated

with a number

of learning

and memory

disorders,such as

Alzheimer’s.

Dr. Volk’s second project focuses on the

protein KIBRA, its interactional partners

and their relationships to learning and

memory. Though KIBRA’s function in the

brain is not fully known, KIBRA’s genetic

mutations and binding partners are

associated with a number of learning and

memory disorders, such as Alzheimer’s. 4-5

A study has also shown that single base

mutations in KIBRA is associated with

variations in human memory—some

people have an allele that is associated

with better memory and some have

an allele that is associated with worse

memory. 6 Therefore, Dr. Volk believes that

KIBRA in humans is likely to be important

in learning and memory regulation. She

has knocked out the KIBRA gene from

mice and discovered that these mice have

impaired learning and memory.

Dr. Volk is also using KIBRA to understand

how information processing at different

levels of scale are integrated. Even with

mathematical models and computational

data, Dr. Volk explains that scientists

cannot predict behaviors of neural

networks if they only know a single

component. “If you have a neuron and

you know everything about how that

neuron works, and then you put a whole

bunch of neurons together, that circuit

of neurons will be able to do things

and have outputs that you wouldn’t be

able to know if you only know how one

neuron functions,” she says. Bridging

the different levels of brain information

processing is important to elucidate the

mechanisms of KIBRA from microscopic

to macroscopic levels. Intracellular

information processing includes calcium

influx and signaling cascades after an

action potential. Synaptic plasticity, the

strengthening or weakening of neuron

synaptic activity in response to changes in

signal or the environment, is a higher level

of information processing that describes

the strength of communication between

two neurons. Circuit-level processing

occurs at the level of a population of

neurons and involves communication and

relationships among multiple neurons.

Behavioral output is the highest level that

scientists can usually observe without

extensive equipment—for example, the

path a rodent takes in a maze to find

food. Dr. Volk and Dr. Pfeiffer are trying to

understand these four different levels of

information processing by manipulating

KIBRA to observe changes in molecular

30 | CATALYST

machinery, synaptic plasticity and

behavior.

The third project in the lab is focused on

analyzing a novel protein that interacts

with KIBRA. “One of the best ways to

understand how a protein functions

is to know what other proteins it

interacts with,” Dr. Volk says. Dr. Volk

and a postdoctoral fellow in the lab, Dr.

Xin Shao, believe that one of KIBRA’s

binding partners is very important to

understanding learning and memory, as

KIBRA has already been implicated to be

abnormally predisposed to be associated

with neurodevelopmental disorders. They

expressed this novel protein in neurons

and discovered it might be killing them.

Dr. Volk jokingly said that this finding did

not excite her, because a dead neurons

“can’t process any information and

can’t do anything about learning and

memory.” However, they proceeded with

the experiments and found two different

versions of the protein: a long and short

version. The short version of the protein

seems to kill neurons while the long

version does not.

Dr. Volk then decided to see if the

novel protein has a role in a natural

pathophysiological condition as opposed

to cultured neurons. She collaborated

with a fellow UTSW faculty member

who worked on stroke, a natural

pathophysiological condition that is

common in people and animals. Stroke

occurs when blood flow to a part of the

brain is restricted and brain cells die from

lack of oxygen. Dr. Volk’s collaborator

induced stroke in some mice and Dr.

Volk discovered that the short version

of the novel protein was dramatically

up-regulated in the brain areas affected

by stroke. By seeing how this protein

affected neurons during stroke, Dr. Volk

and Dr. Shao might obtain molecular

information that they can use to prevent

cell death after stroke.

When commenting on her relationship

and collaboration with her husband, Dr.

Volk says that he has been invaluable

in her projects because he supplies

the technical expertise in their in

vivo recordings in both her sleep and

KIBRA projects. When asked about his

contribution to her KIBRA project, Dr.

Volk says, “One thing the collaboration

has allowed us to do, technically, is to

be able to record from animals where

we’ve deleted KIBRA or manipulated

KIBRA function to understand how it’s

affecting circuit function.” Dr. Pfeiffer’s

technical expertise lies in developing a

recording apparatus that is implanted into

rodent brains and can record hundreds

of neurons in awake, freely behaving

Without

memories,

you’re just

a walking

bag of

cells.

You have no

past, and

no future.

animals to investigate circuit function. The

recording apparatus can record electrical

signals from the HC and other cortical

regions at the same time to understand

communication among them as the

animal learns from its environment, forms

memories and stores them long-term.

Although Dr. Pfeiffer almost exclusively

studies rats because they can do more

complex tasks and their brains are

bigger and easier to record from, he has

miniaturized the recording apparatus so

that it can record in mice. This is beneficial

for Dr. Volk because her projects are

mostly based on mouse models, which

currently have more genetic experimental

manipulation capability than rat models.

Dr. Volk says that she hopes that her

three current projects will help contribute

essential understanding about memory

consolidation across multiple hierarchies

of information processing, and potentially

neurodevelopmental disorders such as

autism and schizophrenia in the future.

When asked why she chose to pursue

neuroscience and learning and memory,

she says: “It’s hard to think of anything

more fascinating or compelling than

trying to understand the things that give

us awareness and sense of self. Without

memories, you’re just a walking bag of

cells. You have no past, and no future.”

Works Cited

[1] Carey, B. No Memory, but He Filled

In the Blanks. The New York Times,

Dec. 6, 2010. https://www.nytimes.

com/2010/12/07/science/07memory.

html?ref=health (accessed February 2,

2019).

[2] Dittrich, L. The Brain That Couldn’t

Remember. The New York Times,

Aug. 3, 2016. https://www.nytimes.

com/2016/08/07/magazine/the-brain-thatcouldnt-remember.html?_r=0

(accessed

February 2, 2019).

[3] Pavlides, C.; Winson, J. J. Neurosci.

1989, 9, 2907-2918.

[4] Corneveaux, J.J. et al. Neurobiol. Aging.

2010, 31, 901-909.

[5] Schneider, A. et al. Front Aging

Neurosci. 2010, 2, 4.

[6] Papassotiropoulos, A., et al. Science.

2006, 314, 475-478.

DESIGN BY Samantha Cheng

EDITED BY Preetham Bachina

CATALYST | 31

MEDICAL MARIJUANA? MORE LIKE

MEDICAL MDMA

PARTY DRUGS AND PTSD

Aruni areti & jackson savage

Abstract

Post traumatic stress disorder, or

PTSD has a long history of treatment

through supportive medications such

as benzodiazepines and serotonin

reuptake inhibitors, both treatments

often yielding temporary results and

lacking long-term solutions. Exposure

therapy, a novel treatment process

including administering microdoses of

MDMA, has recently surged in popularity

in reducing PTSD symptoms long-term.

The purpose of this article is to identify

how MDMA can treat persistent PTSD

symptoms through its ability to provide

patients with heightened openness and

decreased Neuroticism. The review also

covers how MDMA-assisted psychotherapy

patients exhibit an increase in openness

and a decrease in Neuroticism, which

demonstrates an improvement of PTSD

symptoms and causes long-term changes

in personality structure. A landmark study

investigates these symptoms through

a randomized trial of MDMA-assisted

psychotherapy therapy. 1 Symptoms such

as Neuroticism and personality variation

improve due to responses found within

3,4-MDMA-assisted psychotherapy. An

additional study illustrates the long-term

effects of MDMA-assisted psychotherapy

by encompassing a multi-month trial

monitoring 19 subjects with a longterm

follow-up. 3 The study illustrates

that subjects, on average, maintained

statistical and clinical gains in symptom

relief from MDMA-assisted psychotherapy,

as opposed to results from previously

existing treatments. The MDMA,

administered in a therapeutic setting,

provides a balance of stable emotions

including a sense of safety and control,

allowing for more mental stability in

patients diagnosed with PTSD.

Introduction

PTSD, is related to both trauma and

stress, which share common effects

with anxiety and dissociative-disorders.

Symptoms stem from the introduction of

a traumatic event, often linked to serious

injury or the death of a significant other.

Manifestations of the disorder include

severe psychological distress and recurring

dreams or flashbacks depicting the

traumatic event. These reminders of the

event negatively affect mood, cognition,

and reactivity of those affected. Global

likelihood to experiencing a traumatic

event is estimated to be around 50-90% 2 ,

and estimated lifetime risk ranges from

6-10%, with women twice as likely to

develop PTSD as men. 3

Psychotherapy is recognised as the most

effective form of treatment for PTSD.

Within psychotherapy, there are several

treatments that have been successful,

including Cognitive Behavior Therapy

(CBT), Cognitive Processing Therapy (CPT),

Trauma-Focused Cognitive-Behavioral

Therapy (TF CBT), and Eye Movement

Desensitization and Reprocessing (EMDR).

Limited research has been conducted to

track personality changes associated with

PTSD treatment response, as personality

theorists argue that traits are relatively

stable during adulthood. There is

evidence, however, linking PTSD to certain

changes in personality after exposure to

trauma. As an example, Vietnam veterans

demonstrated high Neuroticism scores on

the NEO Personality Inventory (NEO PI). 3

Recently, ±3, 4-

methylenedioxymethamphetamine

(MDMA) has been coupled with

psychotherapy in clinical trials to enhance

therapeutic changes in patients. Initial

results have been promising, highlighting

significant reductions in PTSD symptoms

as well as increased longevity of treatment

effects. Evidence suggests that MDMA

increases prosocial feelings and behaviors,

which directly reduce negative moods and

fear response. For these reasons, MDMA

is considered therapeutic as it induces

increased empathy and affiliation due

to serotonin release, with effects lasting

3-6 hours3. It is important to distinguish

between the controlled use of MDMA and

the commonly abused ‘ecstasy,’ which

has unknown purity and dosage. In a

controlled setting, MDMA has the scope to

provide relief to PTSD victims by providing

them with a sense of safety and control. 4

Methods

The first methods section investigates

purported mechanisms of psychological

change coupled with previously obtained

data on MDMA-assisted psychotherapy.

There is a focus on tracking the

Neuroticism and openness variables of

the Neuroticism, Extraversion, Openness

Personality Inventory-Revised test (NEO

PI-R). Screening consisted of a Structured

Clinical Interview for Axis I Diagnosis

(SCID) module, which identifies borderline

personality disorder, and a Clinician-

Administered PTSD Scale (CAPS) with

at least 50 subjects having treatmentresistant

symptoms from war-related

events. Additionally, subjects that had

CAPS score of greater than 50 (moderate

to severe PTSD symptoms) were

administered serotonin-norepinephrine

reuptake inhibitor (SNRI) and provided

with 6 months of psychotherapy. 3 All

subjects suffering from major medical

conditions, other psychiatric conditions,

substance abuse (screened through a

urine test), or major depression were

excluded. Twenty subjects, entirely

32 | CATALYST

FIGURE 1 FIGURE 2

Caucasian, fit the criteria and were

followed up on once after 2 months.

NEO PI-R measurement was created

through pooling hundreds of traits stated

in a self-report questionnaire, peer ratings,

and other psychological tests to build an

overarching list of factors contributing

to personality traits. An independent

administrator conducted the CAPS test in

an interview format to determine if the

subject met the Diagnostic and Statistical

Manual of Mental Disorders (DSM IV TR)

criteria for PTSD diagnosis3.

The second method details 20 individual

subjects with treatment-resistant PTSD

(related to sexual abuse or assault)

subject to psychotherapy with either

MDMA or a placebo. The drug was

administered during two 8-hour sessions

3-5 weeks apart, accompanied with

bi-weekly sessions without drugs4. The

administration sessions were held in a

comfortable atmosphere, encouraging

participants to focus inward and

alternated with time spent talking to

therapists. All 20 subjects completed the

Long-Term Follow-Up (LTFU) questionnaire

(created by the researchers), and 17 retook

the CAPS and IES-R tests. The study

ranged from 17-74 months after final

MDMA sessions, and 10-74 months after

completion of the questionnaire4.

Both studies utilized a LTFU questionnaire

for use in later evaluations of

MDMA-assisted psychotherapy. This

questionnaire was built to understand and

determine the effects of MDMA-assisted

psychotherapy and changes in quantitative

and qualitative analysis. The LTFU

questionnaire assessed the degree (with

an ordinal scale of 1-Slight to 5-Large) and

persistence (scale of 1-Small to 5-All) of

the perceived benefits and/or harms of

MDMA-assisted psychotherapy for PTSD.

The MDMA provides a

balance of

stable emotions

including a

sense of safety

and control,

allowing for

more mental

stability

in patients diagnosed

with PTSD.

Results

Figure 1 and 2 compare CAPS scale scores

between the placebo and MDMA groups

after treatment. Figure 1 illustrates the

change in Openness as a covariate to

change in CAPS, while Figure 2 illustrates

the change in Neuroticism as a covariate

to change in CAPS. In Figure 1, after

changes in Openness were accounted

for, the effects of MDMA on CAPS scores

were no longer significant. For Figure

2, the MDMA group saw a significant

improvement in CAPS scores compared to

the placebo group3.

Table 1 illustrates descriptive statistics

for the examined group differences in

Openness and Neuroticism at baseline and

2-month follow-up. These results revealed

no main effect within Openness; however,

there was a significant correlation

between Openness and MDMA group,

signifying that there was an increase in

Openness within the MDMA group but a

decrease within the therapy only group

from baseline to follow-up3. In regards

to Neuroticism, there was a significant

main effect on the group, but there was

no seen significant interaction. Moreover,

the follow-up analyses were unable to

find significant group differences for

Openness or Neuroticism at baseline or

2-month follow-up. However, correlational

analysis of the significant changes within

personality traits helped indicate that

across both groups Openness increases,

Neuroticism decreases. 3

Table 2, on the other, hand illustrates

prominent data on mean differences in

Openness and Neuroticism personality

traits at the baseline in comparison to

LTFU following usage of the MDMAassisted

psychotherapy. 3 Such results

CATALYST | 33

explain that were prominent changes

in both Openness and Neuroticism in

comparison to the baseline personality

traits that come up with long-term followup

traits that follow the MDMA-assisted

psychotherapy.

Based on the LTFU questionnaire for use

in LTFU evaluations of MDMA-assisted

psychotherapy, CAPS and IES-R scores at

LTFU for the 16 study completers from

Study 2 were not statistically different

from their 2-month (short-term) mean

scores (Table 3) illustrating similar

explanation and effects toward the

study. Throughout this study, all subjects

reported a benefit from participation in

the study (median = 5, range = 3), with

at least some benefit persisting (median

= 5, range = 3) for longer than a year

post-treatment. Moreover, the 16 LTFU

CAPS completers reported some sort of

degree of benefit (median = 5 (maximum

score possible); range = 3)4. These results

illustrate that there was no clear difference

between the CAPS completers and noncompleters

in terms of the degree of and

persistence of their benefits from the

MDMA-assisted psychotherapy. Even more

striking, all participants answered “Yes”

to the question, “Do you believe more

MDMA sessions would have been helpful”

for further treatment of PTSD. Within this

study, participants stated that there was

either no change or some improvement

in their cognitive function, memory,

and concentration: 7/19 participants

reported no change, while 13 reported

improvements in these areas and none

indicated inhibition or worsened effects.

Overall, participants described the

experimental treatment as being helpful,

sometimes dramatically so (“The therapy

made it possible for me to live”), but also

as being difficult at times (“one of the

toughest things I have ever done”). Several

participants described it as a step in an

“ongoing process” rather than simply a

completed cure. 4

Discussion

The first study concluded that persistent

changes in both Neuroticism and

Openness occurred post MDMA

treatment. Patients experienced

symptom relief for up to 45.5 months

post-treatment. These results allude to

MDMA’s potential to fundamentally alter

personality traits beyond the scope of

PTSD treatment, and result in long-term

changes. The study also determined that

Openness is a key indicator linked to PTSD

symptoms, and those with MDMA assisted

psychotherapy experienced greater

changes in Openness. 3 However, some

scholars argue that personality traits, by

definition, are stable over a lifetime. The

present study and other studies suggest

that certain facets to personality are able

to be manipulated and can be relevant in

reducing PTSD symptoms. 3

The recipients of MDMA-assisted

psychotherapy characterized their

experience as cleansing. They reported

being able to explore new territory within

their mind, leading to increased Openness

and a new perspective on their trauma.

The study did not address the biochemical

aspect of MDMA, instead, the researchers

suggest that MDMA primes a susceptibility

to increased Openness in its recipients,

thus enhancing therapy’s effectiveness.

Individuals with the most change in

Openness also experienced a greater

reduction in PTSD symptoms.

The authors of this paper speculate that

both environmental factors, including

significant trauma and profound

experiences, and epigenetic factors

influence underlying personality aspects.

The question of how MDMA-assisted

psychotherapy can result in long-term

personality changes remains a debated

subject. Further research is required to

investigate what processes can manipulate

personality traits as well as to further

define what facets are encompassed in

personality. 3

Three limitations are outlined in the first

study. The trial was run as a double-blind

trial, however, many participants and

therapists correctly identified their case.

Shifts in expectations towards therapy

may have resulted from this occurrence,

as is suggested by the initial decrease

in Openness but not Neuroticism in the

placebo group3. Second, the findings of

this study rely on subjective reports by the

participants; this limitation is shared by

almost all clinical diagnoses and studies

of PTSD. Last, the sample size was limited,

but clear trends existed within this group. 3

The second study has evidence within the

LTFU study that alludes to the clinically

meaningful benefit from MDMA-assisted

psychotherapy to PTSD patients. When

looking at the final data, one must note

that 3 of the 19 subjects did not complete

the CAPS and IES-R. However, they did

complete the LTFU Questionnaire and

reported nearly the same degree of

benefit and persistence of benefit as those

who had completed the CAPS. These

results illustrate that up to 89% (17/19)

of those who received MDMA had longterm

improvement in PTSD symptoms4.

Overall, the LTFU questionnaire illustrated

some critical points: there is an clear

absence of risk for substance abuse and

neurocognitive decline when juxtaposed

with the clear improvement of symptoms

and other perceived benefits. 4

The paper claims that the data from

the LTFU Questionnaire supports the

hypothesis that MDMA can be utilized

in a clinical setting with limited risk that

participants will subsequently seek

self-administered “street ecstasy,” or

become addicted to the drug. 4 However,

this treatment must be implemented

with several precautions: MDMA being

administered in a therapeutic setting and

close follow-up of patients are essential

elements of the treatment and must be

included with clinical monitoring and

therapeutic support when MDMA is

TABLE 2

TABLE 1

34 | CATALYST

utilized4. MDMA becomes an emotional

distresser of PTSD often contributing

to the usage of intoxicants that act as

an escape at self-medication inhibiting

emotional distress in turn limiting the

subject’s motivation for drug abuse.

Moreover, the data illustrates that there is

improvement and stability within cognitive

function, memory, and concentration.

Evidence for these improvements comes

from a strong correlation between

the positive reports from the LTFU

Questionnaire and the formal evaluations

of cognitive function taken before and

after psychotherapy with MDMA versus

placebo. 4

In addition, there was improvement in

PTSD symptoms documented on the CAPS

alongside other major benefits that have

been reported by the LTFU Questionnaire.

There is additional evidence of positive

MDMA treatment effects extending

beyond the realm of symptom reduction

that are endorsed within the LTFU

Questionnaire and its comments section4.

Many subjects reported benefits that

correlate to improvement within their lives

alongside deeply meaningful therapeutic

experiences such as “increased selfawareness

and understanding” and

“enhanced spiritual life.”4 These comments

illustrates the authentic implication of the

psychological and spiritual exploration

and growth that in turn limit trauma

and symptoms promoting healthy

psychological development. Subjects have

also commented on the nature that the

effects of MDMA have given a certain level

of stability allowing them to gain the tools

to succeed and move on with a great level

of neutrality. 4

Conclusion

These studies were done in attempt to

develop and test a novel therapy for

PTSD, a clinical disorder that is in need

of a wider array of effective treatment

options. Utilizing empirical data from the

LTFU Questionnaire alongside the formal

measures of cognitive function before and

after psychotherapy between MDMA and

placebo, both Mithoefer et al. and Wagner

et al. can report long-term outcome

results in the original cohort. Both results

conclude long-term benefits to their

patients with no cases of subsequent drug

abuse and no reports of neurocognitive

decline with usage of MDMA. These

results illustrate favorable long-term risk/

benefit ratio for the administration of

MDMA in a clinical setting in conjunction

with psychotherapy for PTSD treatment.

With the results of these two studies,

and subsequent research increasing the

data that supports these findings, we

predict MDMA-assisted psychotherapy will

become a viable and accessible treatment

option for PTSD.

Works Cited

[1] Wagner, Mark T, et al. “Therapeutic

Effect of Increased Openness:

Investigating Mechanism of Action in

MDMA-Assisted Psychotherapy.” Journal of

Psychopharmacology, 21 June 2017.

[2] Sascha, Thal B, and Miriam J. J.

Lommen. “Current Perspective on MDMA-

Assisted Psychotherapy for Posttraumatic

Stress Disorder.” Journal of Contemporary

Psychotherapy, 6 June 2018.

[3] Johansen, PØ, and TS Krebs. “How

Could MDMA (Ecstasy) Help Anxiety

Disorders? A Neurobiological Rationale.”

Journal of Psychopharmacology, 2009.

[4] Mithoefer, Michael r C, et al. “Durability

of Improvement in Post-Traumatic Stress

Disorder Symptoms and Absence of

Harmful Effects or Drug Dependency

Journal of Psychopharmacology after

3,4-Methylenedioxymethamphetamine- ©

Assisted Psychotherapy: a Prospective

Long- Term Follow-up Study.” Journal of

Psychopharmacology, 2013.

DESIGN BY Juliana Wang

EDITED BY Natalie Gault

TABLE 3

CATALYST | 35

Plant Communication

SILENT BUT NOT INVISIBLE

by Lani DuFresne

If plants had a language, what would it

sound like? For years, the concept of plant

communication was fairly nonexistent, and

hypotheses about trees sending each other

electrical signals as they were being cut down

were considered lunatic at best [1]. The

botanical world has largely been viewed as a

silent one, but the past few years of research

have finally unveiled the buzz of constant

communication between plants, all unheard

by human ears.

As it turns out, plants need to ‘talk’ to each

other for many of the same reasons humans

have developed verbal and body language:

to coexist successfully, express physiological

needs, and cooperate in protecting

the overall community. Only recent

advancements in technology have allowed

humans to gain insight into this unheard

conversation – and now we can see it as well.

Scientists have managed to visually prove

that plants warn each other of impending

dangers, negotiate with their nearest

neighbors, and send messages throughout

their populations when necessary.

For example, a curious phenomenon

called ‘crown shyness’ refers to the learned

behavior of plants, especially large trees,

to redirect and divert growth when their

leaves begin to brush up against the leaves

of surrounding vegetation [1]. It’s almost the

botanical equivalent of body language. More

common, however, are chemical signals that

spread throughout the body of one plant

and then to those closest to it. Roots of one

plant exude organic compounds into the soil

that then pass into nearby plants through

their roots, giving neighbors information

on each other’s well-being. When tested

on corn seedlings, researchers found that

seedlings would direct growth away from

plants whose roots were emanating chemical

signals of distress in an effort to avoid the

same stressors, and would also rely on these

signals to reorient themselves if they sensed

they were growing too close to each other. 2

The ability of plants to communicate with

each other is crucial in defending against

external threats like herbivory, chemical

pollution, and even lumberjacks. Scientists

had previously inferred that plants could

“...the past few years

of research have

finally unveiled the

buzz of constant

communication

between plants, all

unheard by

human ears.”

warn each other of danger after one

individual was attacked, but molecular

technology has recently provided a

remarkable visual representation of how the

process actually works [3]. When a plant is

attacked – say, by an herbivorous caterpillar

– the site of the wound triggers a release of

glutamate (a neurotransmitter that is also

found in animals), which causes a change

in calcium ion (Ca2+) concentration that

spreads throughout the plant in minutes.

The electrical signal then jumps to other

surrounding plants, resulting in a chain

reaction [4]. In cases such as an attack from

a voracious caterpillar, this rapid alert system

is useful because it allows the undamaged

leaves to quickly mount a defense response,

which usually involves the production of

hormones that make the leaves toxic or

unappetizing [3].

This entire process occurs silently and

is virtually undetectable – or was, until

scientists created a mutated species of

Arabidopsis in which calcium concentrations

could be seen under fluorescent light [4].

The final effect (seen in image) is a visually

stunning reminder of the secret signals that

lie beneath the surface.

Works Cited

[1] The Guardian. Plants ‘talk to’ each

other through their roots. https://www.

theguardian.com/science/2018/may/02/

plants-talk-to-each-other-through-their-roots

(accessed October 24, 2018).

[2] Elhakeem, A.; Markovic, D.; Broberg, A.;

Anten, N.P.R.; Ninkovic, V. Aboveground

mechanical stimuli affect belowground plantplant

communication. PLoS ONE 2018, 13(5):

e0195646.

[3] Interesting Engineering. New Discoveries

Made in How Plants Warn Each Other of

Danger. https://interestingengineering.com/

new-discoveries-made-in-how-plants-warneach-other-of-danger

(accessed October 24,

2018).

[4] Toyota, M.; Spencer, D.; Sawai-Toyota,

S.; Jiaqi, W.; Zhang, T.; Koo, A.J.; Howe, G.A.;

Gilroy, S. Glutamate triggers long-distance,

calcium-based plant defense signaling.

Science. 2018, 361(6407), 1112-1115.

DESIGN BY Priscilla Li

EDITED BY Evelyn Syau

36 | CATALYST

Dark Matter

Mapping

BY KSENIA METRUCK

What if 90% of your furniture was

invisible? You would have to think

of some pretty creative ways to

find it. Personally, I would drape sheets over

everything in my house, great for Halloween

time.

Unfortunately, it would be pretty difficult to

cover all of the invisible matter in the universe

with blankets, they just aren’t big enough.

From what astronomers have discovered, as

much as 90% of what makes up the universe

is completely “invisible.” In other words, it

does not radiate any signatures that can be

detected in the electromagnetic spectrum by

current technology [1].

The good news is that astronomers have

created a few extremely clever ways of

guessing the general mass and location of all

of this dark matter.

Individual galaxies are always evolving

because of the mutual gravitational pull of

their galactic neighbors. But we know that

the gravity caused by visible mass alone

is not enough to stretch across the large

distances between them. The gravity added

by invisible dark matter is the major factor as

we watch many galaxies growing, shrinking,

transforming, and colliding. The paths that

they take allow astronomers to find the

gravitational forces at work on them. From

these forces, we can calculate the mass of

dark matter that the galaxies must contain to

sustain their motions [2].

From what astronomers

have discovered, as much

as 90% of what makes

up the universe is

completely “invisible.”

Another way of searching for dark matter

involves examining the x-rays released by

large dust clouds. X-rays are only detectable

because dark matter between their sources

and where they are detected induce lensing.

Gravitational lensing refers to a phenomenon

where electromagnetic wave, like x-rays, are

pulled slightly towards a large mass which

gives a curve to their path. Because the path

the rays follow can be approximated, any

curves give away the location of large masses,

like dark matter. The amount of dark matter

can be estimated based on the size and shape

of the curve. So far, matter found using this

technique accounts for 20 to 30% of a galaxy

cluster’s total gravitating mass [3,4].

A similar way to detect dark matter involves

spotting rings or arcs around clusters of

galaxies called “Einstein rings”. These rings

are also caused by gravitational lensing,

however, scientists look for waves in the

visible light spectrum as opposed to x-rays. In

order to form a ring, or even a partial ring, the

two objects must be almost perfectly aligned

in relation to the observation point. The light

from the hidden object is then stretched

around the foreground object forming the

light ring seen in the image below [5]. How

well the ring is defined can be useful in

estimating the total mass of the foreground

galaxy [6].

It’s important to find out as much about

where dark matter is located as possible.

Future space missions can take advantage of

these bodies of mass to slingshot spacecrafts

into deep space, but you don’t want any

surprises with billion dollar equipment.

References

[1] http://www.indiana.edu/~geol105/images/gaia_

chapter_1/dark_matter_in_the_universe.htm





[4] https://arxiv.org/pdf/1504.05254v3.pdf

[5] https://www.space.com/33095-nearly-perfecteinstein-ring-discovered-image.html



DESIGN BY Kaitlyn Xiong

EDITED BY Nigel Edward

Image made up from several images taken with the DECam

camera on the Blanco 4m telescope at the Cerro Tololo

Observatory in Chile.

CATALYST | 37

humans: are

we really just

crabby people?

By natalie gault

Iam sure many of us have heard the term

“cut-throat.” A rather negative adjective,

this word describes individuals who

will do anything to succeed - as the name

suggests, even “cutting the throats” of others

to get ahead. While we may not identify with

this harsh term, we may empathize more

with crabs. This comparison may appear

harmless, but the “crab mentality” can be just

as unhealthy as a “cut-throat” perspective.

The crab mentality follows that a lone crab

in a bucket can pull themselves out and

escape. However, with multiple crabs, no

crab can leave: the bottom crabs pull down

those that try to climb their way out. This

seems extremely counterintuitive; however,

the crab mentality is a common analogy and

explanatory model for human society. The

crab mentality can explain many everyday

experiences, thoughts, and behaviors. How

many times have other people silently wished

for us to fail? How many times have we

wanted other people to be unsuccessful? The

crab mentality is a very common, yet often

unacknowledged mindset with significant

consequences, particularly to our own

happiness and wellbeing. Learning about this

phenomenon can allow our metamorphosis

from craps to caring, supportive humans,

and in turn, be much happier. In addition,

understanding the crab mentality can help us

escape any toxic and negative environments

created by the crabs around us.

What makes us hold these negative wishes

for those around us? Why do we want others

to fail? Sam Woolfe states that the crab

mentality can stem from multiple causes,

including but not limited to envy, low selfesteem,

insecurity, and a competitive nature.

We like to think that these thoughts make

us happier because in the moment we do

feel a bit better: if someone else doesn’t

succeed, it means we’re not failing. Yet, while

it may lighten our mood, it is only transient

and actually fuels a continuous cycle of

feeling unworthy and incompetent. Instead

of viewing friends as people we can look up

to and mutually support, the crab mindset

portrays them as competition that we must

beat. What’s worse about the crab mindset

is that it involves multiple crabs: just as you

do with other people, they may do to you.

The environment you’re in may want your

failure just as much as you want them to not

succeed.

The crab mentality

can stem from multiple

causes, including but not

limited to envy, low selfesteem,

insecurity, and a

competitive nature.

However, the crab mentality can be

overcome: you can crawl over the bucket.

If you sense that the network you’re

currently in wants to see you fail, distancing

yourself and finding an empowering group

will help you escape the trap. Some ways

to find these supportive groups include

joining a mastermind group, working with

accountability partners for specific goals,

signing up for classes you’re interested, and

so much more. The crab mentality may feel

like the only option to feel secure in yourself

and your accomplishments, but being happy

for others can actually motivate you and urge

your own success and improvement. With

mutual support and respect, we can all climb

over the bucket.

References

Scott, S. (2019, January 02). What Is the “Crabs in

a Bucket” Mentality? Retrieved from https://www.

developgoodhabits.com/crabs-bucket/

Woolfe, Sam. (2018, July 11). The Crab Mentality:

Why Can’t We Be Happy for Other People’s

Success? Retrieved from https://www.samwoolfe.

com/2018/07/crab-mentality.html

DESIGN BY Evelyn Syau

EDITED BY Evelyn Syau

Graphic from KissPNG

38 | CATALYST

Thank you to our

Catalyst sponsors!

Rice University Center for Civic Leadership

Program in Writing and Communication

Rich Family Endowment

Wiess School of Natural Sciences

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Young Women’s College Preparatory Academy

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