Breakthrough - Winter Edition: December 2021

Winter Edition / December 2021

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The Ramaz Science Journal

The Zipper Con guration - DNA in

Uncovering The Past, One Star at A

Nanoelectronics

by Ron Alweiss ’22 Pg. 3

Time

by Noa Essner ‘25 Pg. 13

Power of Stem Cells Harnessed to

A Possible Cure for Cancer?

Create Cartilage Tissue

by Ariella Goloborodsky ‘23 Pg. 15

by Mia Brodie ’22 Pg. 5

Pig To Human Kidney Transplant

by Sarah Kalimi ‘25 Pg. 17

A Greener Way to Build Molecules Wins the Nobel Prize

by Sydney Eisenstein ’''22 Pg. 8

Tusked or Tuskless; The Changing African Elephant

by Sarah Silverman ‘24 Pg. 19

Astronomers Potentially Stumbled Upon the First Exoplanet Located Outside Our Galaxy

by Noa Essner ‘25 Pg. 11

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Table of Contents

The use of DNA spans from instructing your body how to create proteins to allowing people to reproduce. A less known purpose for DNA is as a conductor of electricity. This offers nanoelectronics a highly conductive current; however, a difficulty stems from the length of the DNA. The conductivity decreases exponentially on a relatively long single-molecule strand of DNA, so only short strands are a viable option as conductors.

Researchers in Japan found a solution, allowing long DNA to be a beneficial conductor. The “zipper” configuration provides a structure where the current can flow and even maintains selfrestoring properties to mend any faulty connections. Dr. Tomoaki Nishino of Tokyo Tech discusses how he studied electron transport through single-molecule DNA and discovered the effective results of the zipper configuration, which is caused by the “orientation relative to the nanogap axis.”

Researchers compared the results of a 10-mer DNA strand to a 90-mer strand (mer refers to the number of nucleotides, which relates to the length as 10-mer is considered a short DNA strand while 90-mer long) to form a zipper configuration. One side is attached to gold (a conductive metal) and the other side to a metal tip of a scanning tunneling microscope, which measures the nanogap between the tip and the DNA strands. The researchers discovered that, in this junction, unconventionally high conductivity in the 90-mer DNA strand is generated, which confirmed their hypothesis about the viability of long DNA in the zipper configuration. To the researchers’ pleasant surprise, they observed the self-restoring quality of the junction as the configuration would go from “unzipped” to “zipped” on its own, repairing itself after an electrical malfunction. This junction surpassed the researchers’ expectations and will allow for more effective and durable nanoscale electric currents, which could revolutionize the nanoelectronic industry!

Ron Alweiss ’22

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The Zipper Configuration - DNA in Nanoelectronics

Harashima, Takanori, et al. “Single-Molecule Junction Spontaneously Restored by DNA Zipper.” Nature News, Nature Publishing Group, 1 Oct. 2021, https://www.nature.com/articles/ s41467-021-25943-3?proof=t.

“Towards Self-Restoring Electronic Devices with Long DNA Molecules.” ScienceDaily, ScienceDaily, 2 Nov. 2021, https://www.sciencedaily.comreleases\2021/11/211102131701.htm.

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References

Cartilage is the tissue that absorbs shock, and trauma in many parts of the body. It's in ears, nose, knees, and virtually every joint in the body. Since cartilage is the main form of protection in the joints where bone meets bone, it gets a lot of wear and tear. This could be from playing sports, running, regular aging or a genetic mutation.

Until now doctors have dealt with cartilage damage by either replacing a joint with metal or by creating microfractures in joints by drilling tiny holes in cartilage to prompt regrowth. However, metal replacement joints are not wholly effective because the metal loosens from wear and tear over time. Micro-fractures are also not full proof because the results are inconsistent: Some people do not heal as well. This method damages an already weakened tissue and sometimes the human body can’t heal quickly enough, or return to as strong a state as the joint requires. Additionally, some patients develop fibrocartilage which is scar tissue in the joint, rather than healthy, strong cartilage.

In recent years scientists and doctors have been working on a technique called stem cell harnessing. Scientists encourage a cell to grow and group, eventually becoming bone. Since bones go through a developmental cartilage phase before hardening into bone, researchers have begun to study how to stop the cell growth at the cartilage phase, and create replacement cartilage.

Even before starting to grow these cartilage cells, researchers had to first study what special molecules and embryonic cells they could specialize and grow. This led researchers in Stanford School of Medicine to utilize a molecule called bone morphogenetic protein 2 (BMP2). In this case, they also created microfractures but used BMP2 to initiate bone regrowth and then stop from continuing to develop during its cartilage phase. This method was successful when tested on small animals and then on larger ones.

The Centre for Human Development used another method of harnessing stem cells. In this case they took embryonic stem cells (which are cells without a specialization), and then specialized them to become cartilage cells.

This research is critical because it is relevant to many millions of people who will have cartilage problems and weakness. According to Dr. Longaker, who is a professor in Stanford Medical

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Power of Stem Cells Harnessed to Create Cartilage Tissues

References McMacken, Melissa. “Joint Repair.” Stem Cell Research at Johns Hopkins Medicine, 21 June 2017, https://www.hopkinsmedicine.org/stem_cell_research/coaxing_cells/joint_repair.html.

“Metal-on-Metal Hip Implant Risks: Arthritis Foundation.” Metal-on-Metal Hip Implant Risks | Arthritis Foundation, https://www.arthritis.org/health-wellness/treatment/joint-surgery/safetyand-risks/metal-on-metal-hip-implant-risks.

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Mia Brodie ‘22

last.

have their knee replaced. This research provides a safe and assured way to remake cartilage that will



School, 1 in every 10 people need a hip replacement by the age of 80, and 1 in every 20 people will

Professor of Surgery (Plastic & Reconstructive Surgery) and (by Courtesy) of Bioengineering and of Materials Science and Engineering.” X, 21 Mar. 2019, https://biox.stanford.edu/people/ michael-longaker.

News Center. “Researchers Find Method to Regrow Cartilage in the Joints.” News Center, 17 Aug. 2020, https://med.stanford.edu/news/all-news/2020/08/Researchers-find-method-toregrow-cartilage-in-the-joints.html.

“Power of Stem Cells Harnessed to Create Cartilage Tissue.” ScienceDaily, ScienceDaily, 28 Sept. 2021, https://www.sciencedaily.com/releases/2021/09/210928074943.htm.

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“Michael Longaker - Deane P. and Louise Mitchell Professor in the School of Medicine and

Two scientists developed a tool that transformed how chemists build new molecules, making the operation faster and more environmentally friendly. To construct a new molecule, atoms must be stitched together in particular orders by a series of chemical reactions. The process of creating these intricately twisted molecules is both wasteful and slow.

Chemists Benjamin List of the Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr, Germany and David MacMillan of Princeton University were awarded the 2021 Nobel Prize in chemistry for revolutionizing the construction of new molecules. They developed organic catalysts to expedite the chemical reactions necessary to build new molecules, a process known as asymmetric organocatalysis.

Creating new drugs or materials often requires the construction of new molecules from simpler molecules. To convert from simpler molecules to new molecules, the simpler chemical building blocks must be precisely arranged through a series of chemical reactions. Many chemical reactions create two versions of a molecule that are mirror images of each other, and frequently have different effects. For example, a drug prescribed in the 1950s and 1960s for morning sickness, thalidomide, caused birth defects in more than 10,000 babies because the mirror image of a molecule was used. Controlling which version of a molecule is used is crucial for successful drug development.

Historically, chemists have known about two types of catalysts - enzymes and metals. Enzymes are clunky proteins which are difficult to use on a large scale in labs. Many metal catalysts, such as cobalt or platinum, are often toxic to the environment and expensive to obtain. Additionally, many metal catalysts only work in airless and waterless environments which are difficult to achieve.

In 2000, List was studying the aldol reaction, which links two molecules using carbon bonds.

This type of reaction in organisms relies on a convoluted and large enzyme known as aldolase A. Although aldolase A is such a large enzyme, only a small part of the enzyme is used to catalyze the reaction. List discovered that proline, an amino acid, could do the work of aldolase A and also create one version of the product much more often than the other version.

At the same time, MacMillan was also looking for alternative catalysts. He studied a chemical reaction known as the Diels-Alder reaction, which forms rings of carbon atoms. The reaction is used

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A Greener Way to Build Molecules Wins the Nobel Prize

catalysts to speed up the slow reaction, but the metal would not work when wet. MacMillan created small organic molecules as an alternative to the metal catalysts; the organic molecules catalyzed the reaction in a simpler way and also favored one version of the product over the other. He coined the term “asymmetric organocatalysis” to describe this new way of catalysis.

Both List’s and MacMillan’s findings have sparked much research in discovering more organocatalysts, which has advanced drug development. Peter Somfai, a chemist at Lund University in Sweden and a member of the Nobel Committee for Chemistry, said in a news conference that approximately 35 percent of the world’s gross domestic product depends on catalysis. Somfai explained, “we now have a new powerful tool available for making organic molecules,” one that is drastically faster and less wasteful compared to previous methods.

Somfai emphasized the significance of discoveries in organocatalysts using neurotoxin strychnine as an example. Prior to organocatalysts, chemists depended on a wasteful process of 29 different reactions where only 0.0009 percent of the initial material became strychnine. With organocatalysts, chemists use only 12 steps to synthesize strychnine and the process is more efficient.

Additionally, toxic metals are not used in organocatalysts, making it a more environmentally friendly way of synthesizing chemicals.

Sydney Eisenstein ‘22

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today to create a broad range of products, from rubber to pharmaceuticals. Chemists used metal

Corryn Wetzel, 2021, “Scientists Behind ‘Ingenious’ Molecule-Building Tool Win Nobel Prize in Chemistry”, Smithsonian Magazine

Jonathan Lambert, 2021, “An easier, greener way to build molecules wins the chemistry Nobel Prize”, ScienceNews

“Nobel in chemistry honors 'greener' way to build molecules”, 2021, phys.org

Press release: The Nobel Prize in Chemistry 2021, “An ingenious tool for building molecules”, The Nobel Prize

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References

Exoplanet Located Outside Our Galaxy A few days ago, a groundbreaking scientific feat was accomplished; astronomers may have discovered the very first exoplanet, or planet not included in our solar system, outside of the Milky Way Galaxy.

This find took place using NASA’s Chandra X-ray Telescope, a very powerful telescope located on a satellite, currently floating around in outer space via control of astronomers down on earth. This discovery was made using a process called transits, which is when an object in space obstructs the light of a star, thereby making its radiation of light very feeble long enough for astronomers to determine whether or not said stellar object is in fact an exoplanet. Using this method, astronomers have already pinpointed over 100 billion exoplanets in our galaxy alone, more specifically, only within 3,000 lightyears (one light year is equivalent to roughly 5.9 trillion miles) from earth.

This discovery is huge, and marks a major milestone of astronomical discovery, as it could potentially open doors to further scientific discoveries outside of our galaxy. Additionally, what is believed to be an exoplanet, located in the Whirlpool Galaxy, some 28 million light-years away from the Milky Way, will have to be validated as a legitimate exoplanet. Astronomers uninvolved with the discovery process will eventually observe the transit process on the so called exoplanet, and determine for themselves the validity of the claim. This is a process used very commonly in any given scientific field, known as peer review. This is when other scientists, or researchers in a specific scientific field, determine whether or not the findings of a discovery are plausible by attempting to attain similar results to the experiment, or in this instance, make the same discoveries as these astronomers.

Unfortunately, the potential exoplanet won't be in the same available position to undergo the transit process for at least another seventy years; however, in the meantime, further research into this exoplanet is most certainly underway.

Noa Essner ’25

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Astronomers Potentially Stumbled Upon the First

Gohd, Chelsea. “Astronomers have found what may be the first exoplanet in another galaxy ever detected.” Space.com, Space, 25 Oct. 2021. https://www.space.com/first-planet-outsidemilky-way-discovery

Nasa.gov editors. “What’s a Transit - Exoplanet Exploration: Planets Beyond Our Solar System.” Exoplanet Exploration: Planets Beyond Our Solar System, Nasa.gov. https:// exoplanets.nasa.gov/faq/31/whats-a-transit/

Space.com staff. “Milky Way Home to 11 Billion Planets.” Space.com, Space, 2 Jan. 2013. https://www.space.com/19103-milky-way-100-billion-planets.html

Buongiorno, Caitlyn. “Found: The First Exoplanet Outside of Our Milky Way.” Astronomy.com, 29 Oct. 2021. https://astronomy.com/news/2021/10/first-exoplanetdiscovered-outside-our-

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References

mpanion%20star.

McClure, Bruce. “How Far is a Light-Year?” Earthsky, Updates on Your Cosmos and world, Facebook, 6 July 2021. https://earthsky.org/astronomy-essentials/how-far-is-a-light-year/ #:~:text=A%20light%2Dyear%20is%20the,miles%20(9.5%20trillion%20km).

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galaxy#:~:text=Astronomers%20believe%20they've%20spotted,a%20more%20standard%20co

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Our universe is about 13.8 billion years old. Subsequent to the Big Bang, and with the progression of around 100 million years, came the creation of the first stars. Fast forward billions of years later, and the stars themselves have evolved, namely through a process referred to by scientists as Stellar Evolution, which describes how stars develop over long periods of time, impacting their overall form, size, and shape. About a week ago, scientists located a bizarre cosmic residuum that is theorized to be the remains of one of our universe’s first stars.

The star was given the name AS0039, and it is located in the Sculptor Dwarf Galaxy.

According to NASA.gov, “A galaxy is a huge collection of gas, dust, and billions of stars and their solar systems, all held together by gravity.” The question however is, what exactly is this “stellar remnant,” and how can we deduce its correlation to earlier stars? The answer lies in its own composition. There are three identified categories of stars: Population One, Population Two, and Population Three, which are classified based on their chemical and material makeup. As it has very little iron and higher amounts of magnesium and calcium, AS0039 falls into the Population Two category, although it contains far lower iron than other stars the category, which means that being the remains of an earlier star is entirely a possibility, although never yet has a Population Three star nor remnant been located. Interestingly enough, in several modern-day galaxies, different amounts of metal have been discovered over periods of time. Whereas metals such as iron are more common in different stellar bodies, this residuum was discovered to have trace amounts of iron, similar to what astronomers believe to be a similar amount of earlier stars, which means that astronomers have just obtained a fraction of one of the first stars, a fragment of our scientific past. Imagine all the possibilities of what we could learn if this remnant were really the remains of something from long ago? Suddenly billions upon billions of years ago doesn’t seem so distant, and in current times, the future of discovery is all the brighter.

Noa Essner ’25

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Uncovering The Past, One Star at A Time

Baker, Harry. “Weird Stellar Remnant May Be from One of the First Stars in the Universe.”

Livescience, Live Science, 22 Oct. 2021. https://www.livescience.com/evidence-of-first-starsinuniverse#:~:text=Astronomers%20have%20 detected%20an%20extremely,years%20from%20the%20solar%20system.

Buongiorno, Caitlyn. “Neuron Stars: A Cosmic Goldmine.” Astronomy.Com, Astronomy.Com, 21 Oct. 2021. https://astronomy.com/magazine/news/2021/10/neutron-stars-a-cosmic-goldmine

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References

Scientific American, 19 Jan. 2009. https://www.scientificamerican.com/article/the-first-starsin-the-un/

NASA.gov editors. “What is a Galaxy? NASA Space Place - NASA Science for Kids,” NASA Space Place - NASA Science for Kids, NASA.gov, 6 Oct. 2021.https://spaceplace.nasa.gov/ galaxy/en/

California News Times editors. “Weird Stellar Remnant May Be from One of the First Stars in the Universe.” California News Times, Astrophysical Journal Letters, 22 Oct. 2021. https:// californianewstimes.com/weird-stellar-remnant-may-be-from-one-of-the-first-stars-in-theuniverse/567660/

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Larson, Richard B., and Volker Bromm. “The First Stars in the Universe.” Scientific American,

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Ever since 2011, science has been advancing in cancer treatments by creating treatments that enhance the immune system’s natural ability to fight cancer, called immunotherapy. The newest immunotherapy drug, CAR T-cell therapy, modifies a patient's T-cells to help the immune system kill cancer cells.

Our immune system works in a way where it recognizes and destroys foreign substances through a specific process. Each foreign substance has a protein called an antigen on its cell’s surface.

Our immune system also has T cells that have proteins called receptors attached to them. The receptors on the T-cells can identify and bind to the foreign antigens, then triggering other parts of the immune system that destroy the foreign cells. The relationship between the foreign antigens and receptors is like a lock and key. Each foreign antigen has a specific receptor that is able to attach to it, and destroy.

Cancer cells also have antigens, with only specific receptors that can bind to them. So, CAR T-cell therapy is designed to ensure that a patient’s cells have the correct receptors to bind to the foreign antigens. In CAR T-cell therapies, T cells are taken from the patient’s blood and genetically modified by adding a man-made gene called chimeric antigen receptor (CAR), which helps the receptor better identify cancer cell antigens. Then, the CAR T-cells are put back into the patient’s blood. The CAR Tcells therapy is extremely individualized for each patient, since different cancers all have different antigens. Each CAR is made for a specific antigen. For example, in certain types of lymphoma cancers, an antigen called CD19 is attached to the cancer cells, so the CAR-T cell therapies made to treat these cancers specifically modify the T-cells so that they will be able to bind to the CD19 antigen, fighting off that specific cancer.

The CAR T-cell process can take multiple weeks. First, the white blood cells, inducing T-cells, are removed from the patient’s blood through a process called leukapheresis. Then, the T-cells are separated from the White blood cells, and altered by adding the gene for the specific CAR they need, transforming them into CAR T cells. The CAR T cells are grown and multiplied in the lab, and once enough cells are made, they are infused back into the patient. Once the CAR-T cells begin binding with cancer cells, they multiply even more, and help the immune system destroy even more cancer cells.

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A Possible Cure for Cancer?

treatment options,” said Yale Medicine pediatric oncologist Niketa Shah, MD. CAR-T cell therapy is beginning to revolutionize cancer treatment, and may even be able to replace other cancer treatments such as chemotherapy in the future!

Ariella Goloborodsky ’23

References https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/ car-t-cell1.html

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy

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“This therapy could help patients who have already tried chemotherapy, or who do not have alternative

Hospitals all around the world have used pig valves to save lives for years. We have been trying for years to do the same thing with their organs, which is called xenotransplantation. Surgeons tried doing this even before we invented Human to Human transplants, but of course they had no luck.

Unfortunately, pigs have a type of sugar in their cells that humans don’t have which causes rejection when put into the body. The difference in our cells made pig to Human transplants seem impossible.

On September 25th, this procedure was done on a woman named Susan Fowler in an attempt to save her life. Fowler came to the hospital in critical condition via helicopter. Since there was no Human kidney available at the moment, with the permission of the family, they decided to temporarily use a pig kidney until a new kidney became available. When PETA, People for the Ethical Treatment of Animals, found out about this, they of course disagreed, but were quickly overruled. Unlike the other trials, this pig was genetically engineered to survive without this sugar, so the Human body wouldn’t reject it. They tested the kidney on a deceased body for two days before transferring it to the patient. Since the trial on the cadaver passed the test of immediate rejection, they were optimistic it would work until they could get another kidney. Sadly, Fowler passed away right before her kidney came. While we are heartbroken for her family, Susan Fowler died in the name of science and thanks to her, we are now on the right path to save countless lives.

Sarah Kalimi ’25

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Pig To Human Kidney Transplant

Lambert, Jonathan. Science News. “What Does the First Successful Pig-To-Human Kidney Transplant Mean” 22 Oct. 2021, https://www.sciencenews.org/article/xenotransplantation-pighuman-kidney-transplant

Rabin, Roni. The New York Times. “In a First, Surgeons Attached a Pig Kidney to a Human, and It Worked” 19 Oct. 2021, https://www.nytimes.com/2021/10/19/health/kidney-transplantpig-human.html

Raugh, Don. Everyday Health. “Pig Kidney Transplant in a Human is Performed” 22 Oct. 2021, https://www.everydayhealth.com/kidney-diseases/first-successful-pig-kidney-transplantin-a-human-is-performed/

Webber, Jemima. Plant Based News. “Surgeons Transplant Pig Kidney Into A Human For The First Time, But Is It Ethical?” 20 Oct. 2021, https://plantbasednews.org/culture/ethics/ transplanted-pig-kidney-human/

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References

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Evolution is happening all around us. It is a constant and ever-present arrow pushing towards the future. Humans hundreds of years ago had different adaptations than humans today. As Charles Darwin explained in On The Origin of Species; "The most important factor in survival is neither intelligence nor strength but adaptability." The traits of our species change depending on our environment and the many factors that surround our lives. This is also true for the many animals affected by the disastrous consequences of climate change and deforestation. One of these creatures, the African Elephant, is losing its most valuable and black marketed trait, its tusks.

The ivory trade is a long-standing and controversial market. To acquire the tusks, one must kill the elephant. The tusks of an elephant are its teeth, and contrary to how humans can pull out their teeth, tusks are directly connected to the animal's skull. To show how serious this problem is, in the 1500s there were about 26 million African elephants on the continent; today there are less than 500,000. If tusks were able to be removed, as in the case of Rhinos, conservationists would have extracted them from all surviving elephants, therefore, putting the ivory trade to a halt. This rapid and human-made crisis has resulted in an evolutionary increase in tuskless elephants. Poachers have no reason to kill a tuskless creature since they cannot benefit from its teeth. An average tusked elephant produces $18,000 for a poacher. Therefore through the process of natural selection, the elephants without tusks' offspring have stayed alive and reproduced resulting in a larger tuskless population. A Princeton University study found that during a war in Mozambique, when the ivory trade was increasingly rampant, the number of elephants plummeted. However, the proportion of tuskless females rose from 19 to 51 percent. The drastic change in this figure is astounding, and many scientists and conservationists have used the proportion of tusked to tuskless elephants to assess how the species is doing in an overall area and if they are getting poached.

Can an elephant live without its tusks? This is the same as asking if a human can live without teeth. It is possible but exponentially difficult. They are used for foraging and self-defense in addition to fighting for female mates. It has been noted by animal researchers that the more protected the African elephant is, the more likely it is to bear teeth. These teeth, affected by natural selection, are drastically smaller than the ones of elephants 200 years ago. Humans, as "masters" of the world's

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Tusked or Tuskless; The Changing African Elephant

one example of natural selection being altered by human intervention.

Sarah Silverman ’24

References National Geographic Society. “The History of the Ivory Trade.” National Geographic Society, 15 Feb. 2013, https://www.nationalgeographic.org/media/history-ivory-trade/.

Nuwer, Rachel. “Disturbing Answers to the Mystery of Tuskless Female Elephants.” Scientific American, Scientific American, 21 Oct. 2021, https://www.scientificamerican.com/article/ disturbing-answers-to-the-mystery-of-tuskless-female-elephants/.

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ecosystems and resources, play a role in many animals' evolutionary stories. The African elephant is

Media Company, 21 Oct. 2021, https://www.theatlantic.com/science/archive/2021/10/ elephants-poaching-war-tusklessness/620447/.

Preston, Elizabeth. “Tuskless Elephants Escape Poachers, but May Evolve New Problems.”

The New York Times, The New York Times, 21 Oct. 2021, https://www.nytimes.com/ 2021/10/21/science/tuskless-elephants-evolution.html.

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Yong, Ed. “African Elephants Evolved Tusklessness Amazingly Fast.” The Atlantic, Atlantic

We, at BreakThrough, celebrate scienti c achievements and are thankful for new developments FACULTY ADVISOR Ms. Lenore Brachot EDITORS Sydney Eisenstein ’''22 Ariella Goloborodsky ’''23

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