James Madison High School sophomore Sid Thakker presents his project on gene editing and nicotine addiction to judges at the 2019 Intel International Science and Engineering Fair.

Sid Thakker’s award-winning science fair project began as many science fair projects do: with a basic observation and a burning desire to learn more.

Like all other 10th grade students enrolled in honors chemistry classes at James Madison High School in Vienna, Thakker was required to participate in the annual science fair competition, but when he decided in June 2018 to experiment with gene-editing technology to better understand nicotine addiction, he did so out of genuine passion and curiosity, not a sense of obligation.

Inspired by the biology class he took during his freshman year of high school, Thakker started researching cigarette and e-cigarette addiction after reading about the issue and observing the behavior at school and around his neighborhood.

The resulting project, titled “The Role of Alpha5 Single Nucleotide Polymorphism on Nicotine Dependence,” earned Thakker the second-place Addiction Science Award from the National Institute on Drug Abuse at the 2019 Intel International Science and Engineering Fair, which was held in Phoenix, Ariz., from May 12 to 17.

Thakker was shocked and thrilled to win an award, but he says the best part of attending ISEF was seeing the work that other students have been doing and getting the opportunity to share his own research with professionals in the field.

“When I heard that the NIDA was coming, I was really excited, because they specialize in drug abuse,” Thakker said. “I was really hoping to be able to meet them, explain my project, and I had the chance to, and I had the amazing opportunity to win one of the awards.”

While Thakker has not been directly affected by nicotine addiction, he became concerned with the issue after realizing how pervasive it is in the general U.S. population, including among people his own age or younger.

According to the U.S. Centers for Disease Control and Prevention, tobacco use is the leading preventable cause of disease and death in the U.S., where nearly 40 million adults smoke cigarettes and about 4.7 million middle and high school students use at least one tobacco product.

With cigarette, cigar, and smokeless tobacco use trending downward, tobacco use among youth is now driven primarily by the popularity of e-cigarettes, which were used by 3.6 million middle and high school students in 2018, an increase of 1.5 million from 2017.

4.9 percent of all middle school students reported using electronic cigarettes within the past 30 days in 2018, up from 0.6 percent in 2011, and high school students reported an increase from 1.5 percent in 2011 to 20.8 percent, or roughly one out of every five students, in 2018, according to CDC data.

A 2016 U.S. Surgeon General report on e-cigarette use among youth and young adults, the first one issued on the topic by a federal agency, determined that, although e-cigarettes generally contain fewer toxicants than combustible tobacco products, they still expose users to chemicals like nicotine that are known to be addictive and have adverse health effects.

Spurred by an interest in tackling the problem of nicotine addiction, Thakker reached out to nearby research centers for assistance and connected with a professor at Georgetown University who was looking into the role that the alpha5 receptor plays in triggering addiction to nicotine.

Alpha5 is a protein subunit of receptors found in organisms, including humans, called nicotinic acetylcholine receptors that studies suggest bind to nicotine. The alpha5 then works through a dopamine reward system to make a person feel good when they smoke or use an e-cigarette, according to Thakker.

Using the gene-editing platform CRISPR/Cas9, Thakker removed a small genetic component from the alpha5 to render the receptor inactive, eliminating the hit of dopamine that comes with consuming nicotine.

“Hypothetically, if I would implement this into humans or to mice…with a knockdown of this receptor, I could help to cure nicotine addiction,” Thakker explained.

The 15-year-old says the process of gene editing was complicated, but so far, his research has shown promising results.

The project earned Thakker the cellular and molecular biology award at the 2019 Fairfax County Regional Science and Engineering Fair and a spot at the International Science and Engineering Fair, which is organized annually by the Society for Science and the Public.

The 2019 ISEF attracted more than 1,800 high school students from 81 different countries.

ISEF judges allocate more than $5 million and some 600 individual team awards representing 22 categories every year, along with approximately $4 million in special awards given by participating corporate, professional, and government sponsors.

Including Thakker, Fairfax County Public Schools had 11 students who collectively won seven category awards and two organizational awards at the international fair, FCPS announced in a news release on May 22.

In the category awards, the trio of Miamar Burgos-Rosario, Saijai Supanklang, and Sarah Syed from Hayfield Secondary School won the microbiology category for a project on harmful algal bloom mitigation.

Thomas Jefferson High School for Science and Technology students Divjot Bedi and Rishabh Misra placed second in embedded systems with a project on prosthetics and machine learning, while fellow Thomas Jefferson student Kaien Yang and Madison’s Justin Hu placed third in the energy: chemical and materials science categories.

Rachel Naidich of TJHSST, David Toomer of Hayfield, and Jerry Wei of Oakton High School each won fourth place in their categories, which were biomedical engineering, computational biology and bioinformatics, and robotics and intelligent machines.

In the organizational awards, Thakker was joined by TJHSST’s Bedi and Misra, who received a second-place award from NASA.

The National Institute on Drug Abuse gave a first-place distinction to Brookings High School freshman Aditya Tummala from Brookings, S.D., for developing a protein-based opioid pill that resists tampering through crushing or melting.

Sophomore Nikita Rohila from Stuttgart High School in Arkansas placed third for her survey of risky behavior, such as alcohol use and physical or gun violence, in adolescents.

“We were astonished at both the quality and quantity of ISEF finalists who qualified for the Addiction Science Award this year,” Friends of NIDA executive committee president and chair Dr. William Dewey said. “We are pleased to support these exemplary high school students and encourage them to consider a career in the field of addiction science.”

In addition to receiving $1,500 for his second-place award, Thakker will join Tummala and Rohila sometime this summer for a tour of NIDA, a visit that will include meeting scientists at the research institute and a presentation of his research.

Thakker says he hopes to continue his research on the alpha5 receptor. After testing his model in cells, he is now ready to start studying mice physiology, which is similar enough to humans that it could indicate whether his gene editing might be effective in addressing nicotine addiction.

Thakker has also reached out to Madison’s principal about the possibility of visiting other schools in Fairfax County for a nicotine addiction awareness program, where he could talk to other students about the dangers of e-cigarettes and other related issues.

“There are a lot of…issues that our world is facing today,” Thakker said. “If a lot of us high schoolers with bright minds were able to really invest our time into these serious issues, I feel like we could have an amazing impact.”

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