Caltech attracts some truly unique individuals from all across the globe with a passion for figuring things out. But there was one young woman on campus this past summer whose journey towards scientific research was uniquely inspiring.
Sultana spent the summer at Caltech in the SURF program, working on next generation quantum error correction codes under the supervision of Dr. John Preskill. As she wrapped up her summer project, returning to her “normal” undergraduate education in Arizona, I had the honor of helping her document her remarkable journey. This is her story:
My name is Sultana. I was born in Afghanistan. For years I was discouraged and outright prevented from going to school by the war. It was not safe for me because of the active war and violence in the region, even including suicide bombings. Society was still recovering from the decades long civil war, the persistent influence of a dethroned, theocratically regressive regime and the current non-functioning government. These forces combined to make for a very insecure environment for a woman. It was tacitly accepted that the only place safe for a woman was to remain at home and stay quiet. Another consequence of these circumstances was that the teachers at local schools were all male and encouraged the girls to not come to school and study. What was the point if at the end of the day a woman’s destiny was to stay at home and cook?
For years, I would be up every day at 8am and every waking hour was devoted to housework and preparing the house to host guests, typically older women and my grandmother’s friends. I was destined to be a homemaker and mother. My life had no meaning outside of those roles.
My brothers would come home from school, excited about mathematics and other subjects. For them, it seemed like life was full of infinite possibilities. Meanwhile I had been confined to be behind the insurmountable walls of my family’s compound. All the possibilities for my life had been collapsed, limited to a single identity and purpose.
At fourteen I had had enough. I needed to find a way out of the mindless routine and depressing destiny. And more specifically, I wanted to understand how complex, and clearly powerful, human social systems, such as politics, economics and culture, combined to create overtly negative outcomes like imbalance and oppression. I made the decision to wake up two hours early every day to learn English, before taking on the day’s expected duties.
My grandfather had a saying, “If you know English, then you don’t have to worry about where the food is going to come from.”
He taught himself English and eventually became a professor of literature and humanities. He had even encouraged his five daughters to pursue advanced education. My aunts became medical doctors and chemists (one an engineer, another a teacher). My mother became a lecturer at a university, a profession she would be forced to leave when the Mujaheddin came to power.
I started by studying newspapers and any book I could get my hands on. My hunger for knowledge proved insatiable.
When my father got the internet, the floodgates of information opened. I found and took online courses through sites like Khan Academy and, later, Coursera.
I was intrigued by discussions between my brothers on mathematics. Countless pages of equations and calculations could propagate from a single, simple question; just like how a complex and towering tree can emerge from a single seed.
Khan Academy provided a superbly structured approach to learning mathematics from scratch. Most importantly, mathematics did not rely on a mastery of English as a prerequisite.
Over the next few years I consumed lesson after lesson, expanding my coursework into physics. I would supplement this unorthodox yet structured education with a more self-directed investigation into philosophy through books like Kant’s Critique of Pure Reason. While math and physics helped me develop confidence and ability, ultimately, I was still driven by trying to understand the complexities of human behavior and social systems.
To further develop my hold on English I enrolled in a Skype-based student exchange program and made a critical friend in Emily from Iowa. After only a few conversations, Emily suggested that my English was so good that I should consider taking the SAT and start applying for schools. She soon became a kind of college counselor for me.
Even though my education was stonewalled by an increasingly repressive socio-political establishment, I had the full support of my family. There were no SAT testing locations in Afghanistan. So when it was clear to my family I had the potential to get a college education, my uncle took me across the border into Pakistan, to take the SAT. However, a passport from Afghanistan was required to take the test and, when it was finally granted, it had to be smuggled across the border. Considering that I had no formal education and little time to study for the SAT, I earned a surprisingly competitive score on the exam.
My confidence soared and I convinced my family to make the long trek to the American embassy and apply for a student visa. I was denied in less than sixty seconds! They thought I would end up not studying and becoming an economic burden. I was crushed. And my immaturely formed vision of the world was clearly more idealized than the reality that presented itself and slammed its door in my face. I was even more confused by how the world worked and I immediately became invested in understanding politics.
The New York Times
Emily was constantly working in the background on my behalf, and on the other side of the world, trying to get the word out about my struggle. This became her life’s project, to somehow will me into a position to attend a university. New York Times writer Nicholas Kristoff heard about my story and we conducted an interview over Skype. The story was published in the summer of 2016.
The New York Times opinion piece was published in June. Ironically, I didn’t have much say or influence on the opinion-editorial piece. I felt that the piece was overly provocative.
Even now, because family members still live under the threat of violence, I will not allow myself to be photographed. Suffice to say, I never wanted to stir up trouble, or call attention to myself. Even so, the net results of that article are overwhelmingly positive. I was even offered a scholarship to attend Arizona State University; that was, if I could secure a visa.
I was pessimistic. I had been rejected twice already by what should have been the most logical and straightforward path towards formal education in America. How was this special asylum plea going to result in anything different? But Nicholas Kristoff was absolutely certain I would get it. He gave my case to an immigration lawyer with a relationship to the New York Times. In just a month and a half I was awarded humanitarian parole. This came with some surprising constraints, including having to fly to the U.S. within ten days and a limit of four months to stay there while applying for asylum. As quickly as events were unfolding, I didn’t even hesitate.
As I was approaching America, I realized that over 5,000 miles of water would now separate me from the most influential forces in my life. The last of these flights took me deep into the center of America, about a third of the way around the planet.
The clock was ticking on my time in America – at some point, factors and decisions outside of my control would deign that I was safe to go back to Afghanistan – so I exhausted every opportunity to obtain knowledge while I was isolated from the forces that would keep me from formal education. I petitioned for an earlier than expected winter enrollment at Arizona State University. In the meantime, I continued my self-education through edX classes (coursework from MIT made available online), as well as with Khan Academy and Coursera.
The answer came back from Arizona State University. They had granted me enrollment for the winter quarter. In December of 2016, I flew to the next state in my journey for intellectual independence and began my first full year of formal education at the largest university in America. Mercifully, my tenure in Phoenix began in the cool winter months. In fact, the climate was very similar to what I knew in Afghanistan.
However, as summer approached, I began to have a much different experience. This was the first time I was living on my own. It took me a while to be accustomed to that. I would generally stay in my room and study, even avoiding classes. The intensifying heat of the Arizona sun ensured that I would stay safely and comfortably encased inside. And I was actually doing okay. At first.
Happy as I was to finally be a part of formal education, it was in direct conflict with the way in which I had trained myself to learn. The rebellious spirit which helped me defy the cultural norms and risk harm to myself and my family, the same fire that I had to continuously stoke for years on my own, also made me rebel against the system that actively wanted me to learn. I constantly felt that I had better approaches to absorb the material and actively ignored the homework assignments. Naturally, my grades suffered and I was forced to make a difficult internal adjustment. I also benefited from advice from Emily, as well as a cousin who was pursuing education in Canada.
As I gritted my teeth and made my best attempts to adopt the relatively rigid structures of formal education, I began to feel more and more isolated. I found myself staying in my room day after day, focused simply on studying. But for what purpose? I was aimless. A machine of insatiable learning, but without any specific direction to guide my curiosity. I did not know it at the time, but I was desperate for something to motivate me.
The ripples from the New York Times piece were still reverberating and Sultana was contacted by author Betsy Devine. Betsy was a writer who had written a couple of books with notable scientists. Betsy was particularly interested in introducing Sultana to her husband, Nobel prize winner in physics, Frank Wilczek.
The first time I met Frank Wilczek was at lunch with with him and his wife. Wilczek enjoys hiking in the mountains overlooking surrounding Phoenix and Betsy suggested that I join Frank on an early morning hike. A hike. With Frank Wilczek. This was someone whose book, A Beautiful Question: Finding Nature’s Deep Design, I had read while in Afghanistan. To say that I was nervous is an understatement, but thankfully we fell into an easy flow of conversation. After going over my background and interests he asked me if I was interested in physics. I told him that I was, but I was principally interested in concepts that could be applied very generally, broadly – so that I could better understand the underpinnings of how society functions.
He told me that I should pursue quantum physics. And more specifically, he got me very excited about the prospects of quantum computers. It felt like I was placed at the start of a whole new journey, but I was walking on clouds. I was filled with a confidence that could only be generated by finding oneself comfortable in casual conversation with a Nobel laureate.
Immediately after the hike I went and collected all of the relevant works Wilczek had suggested, including Dirac’s “The Principles of Quantum Mechanics.”
With a new sense of purpose, I immersed myself in the formal coursework, as well as my own, self-directed exploration of quantum physics. My drive was rewarded with all A’s in the fall semester of my sophomore year.
That same winter Nicholas Kristoff had published his annual New York Times opinion review of the previous year titled, “Why 2017 Was the Best Year in Human History.” I was mentioned briefly.
It was the start of the second semester of my sophomore year, and I was starting to feel a desire to explore applied physics. I was enrolled in a graduate-level seminar class in quantum theory that spring. One of the lecturers for the class was a young female professor who was interested in entropy, and more importantly, how we can access seemingly lost information. In other words, she wanted access to the unknown.
To that end, she was interested in gauge/gravity duality models like the one meant to explain the black hole “firewall” paradox, or the Anti-de Sitter space/conformal field theory (AdS/CFT) correspondence that uses a model of the universe where space-time has negative, hyperbolic curvature.
Unbeknownst to me, a friend of that young professor had read the Times opinion article. The article not only mentioned that I had been teaching myself string theory, but also that I was enrolled at Arizona State University and taking graduate level courses. She asked the young professor if she would be interested in meeting me.
The young professor invited me to her office, she told me about how black holes were basically a massive manifestation of entropy, and the best laboratory by which to learn the true nature of information loss, and how it might be reversed. We discussed the possibility of working on a research paper to help her codify the quantum component for her holographic duality models.
I immediately agreed. If there was anything in physics as difficult as understanding human social, religious and political dynamics, it was probably understanding the fundamental nature of space and time. Because the AdS/CFT model of spacetime was negatively curved, we could employ something called holographic quantum error correction to create a framework by which the information of a bulk entity (like a black hole) can be preserved at its boundary, even with some of its physical components (particles) becoming corrupted, or lost.
I spent the year wrestling with, and developing, quantum error correcting codes for a very specific kind of black hole. I learned that information has a way of protecting itself from decay through correlations. For instance, a single logical quantum bit (or “qubit”) of information can be represented, or preserved, by five stand-in, or physical, qubits. At a black hole’s event horizon, where entangled particles are pulled apart, information loss can be prevented as long as less than three-out-of-five of the representative physical qubits are lost to the black hole interior. The original quantum information can be recalled by using a quantum code to reverse this “error”.
By the end of my sophomore year I was nominated to represent Arizona State University at an inaugural event supporting undergraduate women in science. The purpose of the event was to help prepare promising women in physics for graduate school applications, as well as provide information on life as a graduate student. The event, called FUTURE of Physics, was to be held at Caltech.
I mentioned the nomination to Frank Wilczek and he excitedly told me that I must use the opportunity to meet Dr. John Preskill, who was at the forefront of quantum computing and quantum error correction. He reminded me that the best advice he could give anyone was to “find interesting minds and bother them.”
I spent two exciting days at Caltech with 32 other young women from all over the country on November 1st and 2nd of 2018. I was fortunate to meet John Preskill. And of course I introduced myself like any normal human being would, by asking him about the Shor factoring algorithm. I even got to attend a Wednesday group meeting with all of the current faculty and postdocs at IQIM. When I returned to ASU I sent an email to Dr. Preskill inquiring about potentially joining a short research project with his team.
I was extremely relieved when months later I received a response and an invitation to apply for the Summer Undergraduate Research Fellowship (SURF) at Caltech. Because Dr. Preskill’s recent work has been at the forefront of quantum error correction for quantum computing it was relatively straightforward to come up with a research proposal that aligned with the interests of my research adviser at ASU.
One of the major obstacles to efficient and widespread proliferation of quantum computers is the corruption of qubits, expensively held in very delicate low-energy states, by environmental interference and noise. People simply don’t, and should not, have confidence in practical, everyday use of quantum computers without reliable quantum error correction. The proposal was to create a proof that, if you’re starting with five physical qubits (representing a single logical qubit) and lose two of those qubits due to error, you can work backwards to recreate the original five qubits, and recover the lost logical qubit in the context of holographic error correcting codes. My application was accepted, and I made my way to Pasadena at the beginning of this summer.
The temperate climate, mountains and lush neighborhoods were a welcome change, especially with the onslaught of relentless heat that was about to envelope Phoenix.
Even at a campus as small as Caltech I felt like the smallest, most insignificant fish in a tiny, albeit prestigious, pond. But soon I was being connected to many like-minded, heavily motivated mathematicians and physicists, from all walks of life and from every corner of the Earth. Seasoned, young post-docs, like Grant Salton and Victor Albert introduced me to HaPPY tensors. HaPPY tensors are a holographic tensor network model developed by Dr. Preskill and colleagues meant to represent a toy model of AdS/CFT. Under this highly accessible and world-class mentorship, and with essentially unlimited resources, I wrestled with HaPPY tensors all summer and successfully discovered a decoder that could recover five qubits from three.
This was the ultimate confidence booster. All the years of doubting myself and my ability, due to educating myself in a vacuum, lacking the critical feedback provided by real mentors, all disappeared.
Now returning to ASU to finish my undergraduate education, I find myself still thinking about what’s next. I still have plans to expand my proof, extending beyond five qubits, to a continuous variable representation, and writing a general algorithm for an arbitrary N layer tensor-network construction. My mentors at Caltech have graciously extended their support to this ongoing work. And I now dream to become a professor of physics at an elite institution where I can continue to pursue the answers to life’s most confusing problems.
My days left in America are not up to me. I am applying for permanent amnesty so I can continue to pursue my academic dreams, and to take a crack at some of the most difficult problems facing humanity, like accelerating the progress towards quantum computing. I know I can’t pursue those goals back in Afghanistan. At least, not yet. Back there, women like myself are expected to stay at home, prepare food and clean the house for everybody else.
Little do they know how terrible I am at housework – and how much I love math.
Accelerating egg yolks shed light on brain injuries
New insights into how brain injuries occur have been gleaned from a simple study of how an egg yolk is deformed when rotational forces are applied to its outer shell. The experiments were done by Ji Lang, Rungun Nathan and Qianhong Wu at Villanova University in the US, who conclude that brain injuries are far more likely to result from rotational impacts on the skull than from direct translational impacts. Their work provides new insights into how soft matter behaves and could lead to a better understanding of how certain sports injuries occur.
In living organisms, it is common to find highly deformable soft matter that is bathed in a liquid and enclosed in a rigid container. A familiar example is the human brain, which is surrounded by a thin layer of cerebrospinal fluid and encased in a hard skull. It is now widely believed that sudden translational and rotational impacts on the skull will temporarily deform the soft brain, potentially causing serious injury as intricate networks of neurons are disrupted. To study these impacts in further detail, Wu’s team exploited the similarities between the brain with a simpler system: a soft egg yolk surrounded by fluid white and encased in a hard eggshell.
Past studies have explored how soft matter deforms in response to rapidly changing shear and spinning forces in surrounding fluids. Wu and colleagues extended this research by looking at how egg yolks deform during non-destructive translational and rotational impacts on their outer shells. To do this, they devised a simple experiment involving a kitchen gadget that scrambles an egg in its shell. This allowed the team to subject yolks to a variety of shear and spinning flows and image their deformation over time.
The images revealed that the yolks only deformed slightly in response to translational impacts but were highly sensitive to rotational impacts – particularly those involving deceleration. In this case, the researchers determined that the fluid pressure outside the yolk initially becomes larger than the centrifugal force of the fluid enclosed by its delicate membrane, leading to compression at the centre of the yolk. However, if the outer shell’s rotation suddenly stops, these centrifugal forces will become far greater than the outside pressure. This means the yolk will no longer hold its shape and will expand into the surrounding fluid.
New helmet material could protect against glancing blows
The team’s results offer new insights into why brain injuries appear to be more likely to occur after certain types of impact, particularly in sports. Here, rapid rotational decelerations can occur in situations ranging from a boxer’s uppercut to the chin, to impacts on irregularly shaped helmets, like those used in ice hockey. The research may also inform future studies of membrane-enclosed soft matter, including red blood cells and spinning droplets.
The research is described in Physics of Fluids.
MR-Linac verification with RadCalc
Join the audience for a live webinar at 7 p.m. GMT/1 p.m. CDT on 23 February 2021 exploring how RadCalc can improve accuracy, efficiency, and safety in the QA process for MR-Linacs Unity and ViewRay
Want to take part in this webinar?
Participants to this webinar will learn how RadCalc can improve accuracy, efficiency, and safety in the QA process for MR-Linacs Unity and ViewRay.
Hosted by Kathie Carrington, you will:
- Learn about the automated workflow of RadCalc.
- Find out more about the use of RadCalc verifying MR.
- Take part in a question and answer session.
Want to take part in this webinar?
Kathie Carrington is director of applications and training at LifeLine Software, Inc. Company of LAP Group. She has more than 25 years of radiation oncology experience, having held positions from radiation therapist, dosimetrist and department director. She joined Lifeline Software in 2012 and has been connecting radiation therapy departments with software that increases productivity and safety ever since.
CAR-T cells turned into molecular computers destroy tumours more effectively
One of the biggest challenges in cancer therapy is to develop drugs that are as selective as possible, so as to target cancer cells while leaving healthy surrounding tissues intact. Over the last decade, the development of chimeric antigen receptor (CAR) T cell-based immunotherapies has brought us significantly closer to solving this challenge. These therapies involve collecting from a patient’s blood the immune system T cells responsible for identifying and killing cancer cells, and engineering them to produce new surface proteins (CAR) that recognise specific markers – antigens – on the tumours. Once reinjected into the patient’s bloodstream, these CAR-T cells can identify and attack cancer cells more effectively.
While CAR-T cells have proved efficient for treating blood cancers such as leukaemia and lymphoma, solid tumours, such as found in the breast, liver or lung, have been more difficult to vanquish. Many of the markers characteristic to those tumours are also found in normal tissues, causing the destruction of both, as CAR-T cells do not distinguish between healthy and diseased cells. The challenge has hence shifted from “how do we target cancer cells” to “how do we do this while ensuring healthy tissues are left unharmed”.
A possible approach has recently been presented in two complementary articles by Wendell Lim’s research group at University of California San Francisco and Olga Troyanskaya’s group at Princeton and the Flatiron Institute of the Simons Foundation. The researchers combine machine learning and cell engineering techniques to create CAR-T cells that, instead of recognising just one antigen, use Boolean logic (AND, OR and NOT operators) to target combinations of up to three antigens. For example, if antigens A and B are mostly found in tumours but can also be present in healthy cells, while C is only found in normal tissues, the combination “A” OR “B” AND NOT “C” would help differentiate the tumour from normal tissues.
“Currently, most cancer treatments, including cell therapies, are told ‘block this’ or ‘kill this’,” explains Lim. “We want to increase the nuance and sophistication of the decisions that a therapeutic cell makes.”
Preventing off-target killing of healthy cells
In the first article, published in Cell Systems, the researchers investigated the efficiency of antigen combinations to distinguish normal and cancerous tissues in a database of the human genome containing 2358 antigens. A clustering-based score sorted over 2.5 million antigen pairs and approximately 60 million triple antigens. Pairing antigens using either AND or NOT logic gates significantly improved tumour recognition, outperforming well-established single antigens already investigated clinically, in 33 tumours and 34 normal samples.
These Boolean instructions can be programmed into CAR-T cells via synthetic Notch receptors (synNotch), one of the latest developments in cell engineering. Briefly, when a protein binds the Notch receptor, a portion of the receptor breaks off and heads for the cell nucleus, where it acts as a switch to turn on other genes. This allows cells to behave like molecular computers that can sense their environment and then integrate that information to make decisions.
To prove the accuracy of the method, the researchers programmed synNotch receptors to recognise two markers found in kidney tumours, CD70 and AXL, using an AND gate. Targeted separately, CAR-T cells would result in off-target damage, as CD70 is also widely present in healthy blood cells and AXL can be found in healthy lung tissues. But targeting both using an AND gate not only suppressed their expression in tumours in vitro, it also ensured that normal tissue containing just one of these antigens were left unharmed. For example, Raji B cells, which are found in the blood and express CD70, had a survival rate close to 100% with the two antigens, while only around 20% survived when only CD70 was targeted.
Adding a third antigen in the combination helped improve the overall performance across several types of tumour. It also revealed the importance of NOT gates, with 92 of the top-100 combinations of gates for each cancer having at least one such gate. This further highlights the importance of NOT gates in preventing toxic cross reactions, while also significantly improving the correct identification of challenging tumours, such as cholangiocarcinoma, a type of cancer that forms in bile ducts.
New killing strategies
In a second study, published in Science, Lim’s research team expanded on their initial work and daisy-chained multiple synNotch receptors to create a host of complex cancer recognition circuits. The “plug-and-play” nature of synNotch enabled them to customize circuits with diverse Boolean functions, allowing for precise recognition of diseased cells and a range of responses when those cells are identified.
Such circuits can be used in complex scenarios. For example, an antigen localized on the surface of a cell can be targeted, and the decision whether or not to launch the killing process would then be tied to the presence of a second cancer antigen inside the cell. Since CAR-T cells are usually restricted to recognising extracellular antigens, which only represent about 25% of a cell proteome, resorting to this Boolean logic enables targeting of new cancer antigens. As the researchers demonstrated in vitro with melanoma cells, this dual intracellular–extracellular targeting approach both improved specificity and reduced off-target killing.
Blue light activates antibodies on demand
In vivo experiments also showed promising results. The researchers injected a mouse presenting different tumours in each flank – one with two antigens, one with the same two antigens plus an additional third – with a three-antigen-AND-gate T cell composed of three sequentially linked receptors. Allowed to autonomously explore and act on both tumours, the T cells rapidly cleared the three-antigen tumours while ignoring the two-antigen tumours on the opposing flank, similarly to the results observed in vitro.
The possibilities are endless as these smart cells can be designed to fight all kind of tumours. Lim’s group is now exploring how these circuits could be used in CAR-T cells to treat glioblastoma, an aggressive form of brain cancer that is nearly always fatal, using conventional therapies.
“You’re not just looking for one magic-bullet target. You’re trying to use all the data,” Lim says. “We need to comb through all of the available cancer data to find unambiguous combinatorial signatures of cancer. If we can do this, then it could launch the use of these smarter cells that really harness the computational sophistication of biology and have real impact on fighting cancer.”
Joe Biden’s inauguration: why the rebuilding of trust in science is not over yet
The inauguration of Joe Biden as the 46th US President doesn’t necessarily herald a new day for science, cautions Robert P Crease
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