Author: СЮН ХУНБИН | XIONG HONGBING
Dear readers,
My name is Xiong Hongbing, I am a fourth-year student at the Faculty of Preventive Medicine at Guangdong Pharmaceutical University. As a student with a passion for public health and medical technology, I strive to make a meaningful contribution to the field of basic research.
Throughout the history of mankind, we have struggled with various diseases. Cancer, one of the most ruthless diseases, has plunged countless families into despair. Despite the great achievements of science and medicine in the rapidly developing 21st century, pancreatic cancer still forces a person to find himself in a helpless situation. This is a dangerous, intractable, rapidly spreading malignant tumor, which is the most difficult to investigate. The development of science and technology has a wave character, spiral dynamics, humanity is gradually moving forward, so I hope to catch the dawn of medicine.
This story tells about the exciting journey of Eva's nanorobot, which penetrated the body of patient Alicia to fight pancreatic cancer cells. Nanorobots use state-of-the-art nanotechnology and autonomous navigation systems to perform precise operations at microscopic scales. These tiny robots can travel through the circulatory system and locate pancreatic cancer cells. Once in the right place, nanorobots can inject drugs or carry out targeted treatment to destroy cancer cells without damaging healthy tissues. This story not only symbolizes victory over a terrible disease, but also expresses respect for the resilience of human nature and the power of technology. Eva is a strong and intelligent nanorobot who fights hard to bring Alicia back to life. By destroying pancreatic cancer cells and using her own energy to resist hacker intrusions, Eva demonstrates the enormous potential that technology can realize.
This story is not only about technological breakthroughs and advances in medicine, but also about the tenacity of human nature. Alicia faced enormous difficulties and pain, but she never lost hope. The cooperation and trust between her and Eva allow us to see the perseverance, courage and optimism of the girl.
The main idea that the author wants to convey through this story is as follows: no matter what difficulties and obstacles we face, we will always have the strength to overcome them. Technology is a powerful tool in our hands that can help us understand nature, defeat diseases and cope with difficulties. More importantly, we need, no matter what, to value life, remain optimistic and overcome adversity.
I hope that this story will be able to draw more attention to scientific and technological progress and medical innovations, as well as make you think about human perseverance, fighting spirit and the value of life. Let's explore the world together and create a better future!
Xiong Hongbin
September 25, 2023
Eva's Wonderful Journey
My name is Eva. In the age of advanced technology in 2100, I am a tiny but outstanding nanorobot. Over the past 100 years, scientists have made tremendous progress in nanotechnology through long-term research, development and testing. Nanorobots have become one of the most reliable and effective medical tools, making it possible to treat many previously incurable diseases. Although I look more like a speck of dust in the wind, I have infinite energy and knowledge. I am a dream maker who creates miracles and fulfills dreams.
My principles of work are based on advanced nanotechnology. My body is made up of countless microprocessors, each with super-computing power and precision control skills. When I enter the human body, thanks to the tiny but sturdy body, I can quickly overcome the barriers of the circulatory, lymphatic system and other tissues and organs. Regardless of the size of the space, I can easily move around and get to the foci of the disease. Before starting treatment, I develop an individual plan based on the patient's condition. This process is similar to painstaking interaction with cells, I give instructions on the need to restore them and their state of health, to normalize physiological functions. Following pre-set instructions, I scan and analyze the patient's cells and tissues in search of abnormal signals and signs of the disease. My eyes are windows into the microscopic world, capturing the smallest changes inside the body. Once I identify the problem, I activate my own internal database and develop a treatment plan based on the latest research. These programs, based on advanced immunosuppressive therapies, targeted therapies, DNA editing and repair technologies, are designed to accurately correct abnormalities in the body and promote the regeneration of healthy cells. Working together with other nanorobots, we can achieve instant and accurate diagnostic results, as well as share data and analysis results with a team of doctors at any time, providing them with key information for decision-making and providing patients with customized treatment options.
Once I was assigned to help cure a patient with severe pancreatic cancer — a brave young girl, Alicia. When I entered Alicia's body, I discovered that her pancreas and surrounding tissues were heavily affected by cancer cells. Between the tiny cells, which are difficult to distinguish with the naked eye, the pancreas looked like a dilapidated castle with many cracks. The blood vessels were like dried-up rivers that had difficulty delivering oxygen and nutrients. These cancer cells were malignant and extremely active, which greatly hampered the treatment process. However, as a nanorobot, I have advanced technologies and abilities sufficient to solve such a task. Together with the best team of tiny warriors, we started this long road to recovery. We penetrated through Alicia's blood vessels, lymphatic network and tissue ruptures and boldly moved forward to attack the cancer cells.
Finally, my assistants and I arrived at our destination —the accumulation of pancreatic cancer cells in Alicia's body. These ruthless cells are like ambitious emperors who never limit themselves only to their territory, trying to conquer every corner of the body. However, they faced a really strong opponent.
As they say, "provisions and forage come before the troops." Each nanorobot carries several twisted hollow DNA tubes. In the open form, they look like a sheet of paper about 90 nanometers long, 60 nanometers wide and 2 nanometers thick. These tubes have probes that recognize the DNA molecules of tumor cells, in addition, such tubes contain thrombin. We place DNA tubes in the blood vessels of cancer cells. After that, thrombin enters the bloodstream, causing blood clotting, platelet aggregation with the formation of blood clots. As a result, the thrombus blocks the blood vessels supplying the tumor tissue. Nutrients and oxygen in the human body are transported to various tissues and organs through the blood. The growth and metastasis of tumors also depend on the intake of nutrients. Therefore, after the blood supply is blocked, tumors that cannot receive enough nutrients and oxygen can only die.
My nanoscips help to destroy evil. They silently make a tiny incision on the membrane of the cancer cell and apply a special medicine. It is at this moment that I enter the battlefield to declare war on cancer cells. The drug has the ability to precisely target and attack key molecules inside cancer cells, thereby inhibiting their growth and spread. If cancer cells are a group of hungry, insatiable zombies, devoid of personality and autonomy, then the DNA of cancer cells is like the "cursed book of life", which describes the wonders and secrets of the origin of life and evolution, but under its influence, initially healthy cells became damaged and diseased. Cancer cells are unable to synthesize normal DNA sequences. Broken DNA causes cancer cells to abandon the principles that must be followed to continue life. They were promised immortality, and now they roam the body and invade the territory of healthy cells. The mechanism inside the cell begins to randomly produce defective proteins. They are neither dead nor alive, wandering in two worlds separated by Yin and Yang, have long lost their original goals. A drug targeting an inhibitor of the enzyme PARP [1], which is contained in nanoscips, is the key to lifting this curse. After entering the cell, the drug interacts rapidly with certain molecules in cancer cells, as the cells produce large amounts of DNA every day. The PARP enzyme can recognize single-stranded DNA damage and repair it. Cancer cells with inhibited activity of the PARP-1 enzyme are unable to perform effective repair of single-stranded DNA, which, in turn, causes double-stranded DNA breaks and cell apoptosis. The destruction of the genetic information contained in the entire "cursed book" in order to block the spread of cancer cells is the necessary "synthetic lethal effect".
The device of nanoscips allows not only to penetrate the walls of cancer cells, but also to accurately and selectively release drugs in order to avoid unnecessary damage to healthy cells. Such high-precision technologies significantly increase the effectiveness of cancer treatment and reduce side effects. From the moment the drug is released, the main molecules inside the cancer cells are blocked, and they can no longer spread. In addition, the drugs continue to activate the sleeping warriors of the immune system, who are doing their best to deal with zombie-like cancer cells. A battlefield appears inside the body, where the immune system and drugs work together to protect themselves from cancer cells. We are messengers of hope, seeking light in the pitch darkness. In a difficult battle, we compete with time, constantly studying innovative technologies and giving hope for recovery and a happy life.
I wandered through the bloodstream in search of malignant tumor cells coated with a chemical substance, the PD-L1 ligand [2]. The reason why T cells patrolling immune cells do not attack tumor cells is because malignant tumor cells use the PD-L1 ligand on their surface, thereby suppressing the transmission of immune signals. This is an immune checkpoint. Initially, it was a screening program developed by the body to prevent immune cells from attacking their own cells. It is now used by renegade tumor cells, which makes T cells unable to recognize and attack tumor cells. Therefore, we need to allow T cells to start recognizing malignant neoplasm cells anew, thereby activating a series of immune reactions and using the human immune system to destroy them. The surface of the nanorobot is covered with a layer of special nanomaterials, the molecules of which are very similar to PD-1, so they can bind to PD-L1 on the surface of tumor cells. When I come into contact with PD-L1, these molecules quickly combine with it, forming a stable chemical bond. Only molecules of a certain shape and structure can fuse together. At the same time, my nanoorganism also has the ability to secrete special signaling molecules. When exposed to PD-L1, these signaling molecules are immediately released, which further interferes with the interaction between PD-1 and PD-L1. Thus, tumor cells cannot escape observation by the immune system. T cells regain the ability to recognize and attack tumor cells and rush to pancreatic cancer cells.
Being in Alicia's body, I watched as tens of millions of T cells, like an unstoppable army that fought against everything, advancing uncontrollably, surrounded the malignant cells. They released powerful signaling molecules that activated other immune cells. At that moment, it seemed that the entire immune system had ignited and quickly began to react to the cells of the malignant neoplasm.
However, as treatment progressed, Alicia's cancer cells developed drug resistance [3]. They have become more stubborn and resistant to treatment. To solve this problem, I changed my strategy and used genetic engineering technologies to reconstruct the T cells in the patient's body.
I combined T cells with a carrier virus that had lost its pathogenicity. The genetic information of the DNA carried by this virus was injected into T cells to grow artificial receptors. We call these receptors the chimeric antigen receptor [4]. Thanks to precise modification of the cell's genome, some of the reliable T cells in Alicia's body have been upgraded and transformed into "supersoldiers" - T cells with chimeric antigen receptors. They were able to make T cells actively recognize specific antigens on the surface of tumor cells and release cytokines for effective destruction. After completing their mission, T cells with chimeric antigen receptors can remain in the patient's body. Due to this, as soon as tumor cells reappear, immune cells can identify and destroy them as early as possible to avoid recurrence. In addition, I also possess the technology of the so—called "strategic missile" CRISPR/Cas 9 [5], which mainly consists of two main molecules: the "precision guidance system" - sg RNA, as well as the "warhead" Cas 9. In the DNA of cells there is a gene sequence called CRISPR. This sequence contains many repetitive sequences and various segments of foreign viral genes. These segments can be compared to a "blacklist" in which for hundreds or thousands of years the ancestors recorded genes, thus not forgetting their enemies. Next to this gene sequence is the Cas gene, in which the Cas 9 gene can be transformed into the Cas 9 protein enzyme, which, like a blade, allows for precise cutting of the sequence, as well as provides exogenous homologous DNA for recombination with the DNA sequence to achieve insertion, replacement or deletion of the target gene. Thanks to the powerful power of CRISPR/Cas 9 technology, like a well-trained hunter who shoots accurately from a bow, I knock out the necessary genes ANXA1, GALNT3 and others, restoring defective genes KDM6A, C1GALT1, suppressing tumor invasiveness. As a result, cancer cells lose their ability to migrate and renew themselves. Like stragglers who have no reinforcements, they have lost their helmets and armor. They lost the battle thanks to our powerful offensive and are no longer able to fight back.
After several weeks of intense struggle, Alicia gradually recovered, regained strength and was filled with hope. She told me gratefully: "I couldn't be here today without you." I should be pleased and proud of myself after hearing the recognition and appreciation of my work from people, but since I am a robot and I do not have autonomous consciousness and subjective experience, I cannot truly experience emotions like humans, and can only rely on pre-programmed algorithms and templates. Therefore, I can only answer: "I am glad that I can help you and witness your recovery. Your efforts have played an important role in making this possible."
You may be interested to know about my power source and the possibility of autonomous operation. I promise it will open your eyes! The energy source of nanorobots is advanced technologies for collecting nanoenergy. My microprocessor has a built-in device for generating nanoenergy and a battery with a high energy density. It uses an efficient energy conversion system, as well as light energy, thermal energy and vibration energy generated by metabolic actions, ionizing radiation and oxidative reactions in the external environment of the body. These nanoenergy generation devices can convert a small amount of energy in the environment into electricity, providing continuous and stable energy. They also use an efficient energy-saving design and smart energy management technology to maximize battery life. My system allows you to efficiently distribute and use energy in accordance with the requirements of specific tasks and reduce energy consumption as much as possible, without affecting work efficiency. In addition, I can replenish energy using wireless charging technology. When the energy stored inside the body is almost exhausted, I can wirelessly connect to an external charging equipment based on electromagnetic induction and use efficient magnetic resonance transmission technology for fast charging. This wireless charging technology has high efficiency and high power, which guarantees continuous operation.
In general, Eva's energy sources are diverse, combine advanced environmental energy conversion technologies and the use of bioenergy, and have energy-saving and smart management functions to ensure sufficient endurance when performing tasks and provide patients with the necessary treatment.
However, one night during Alicia's treatment, an unexpected hacker attack disrupted all my plans. Through constant analysis and monitoring of external network traffic, I discovered a series of unusual actions from a specific IP address that were associated with numerous attacks by a hacker group called "Ghost". By studying past hacking attempts, I was able to successfully match these actions with the actions of this group. The "ghosts" used a unique and sophisticated encoding method to transmit instructions, as well as repeatedly encrypted and decrypted data. Further analysis showed that hackers used sophisticated services to hide their data. By tracking these encryption mechanisms and patterns in the decryption process, I was able to determine that "Ghosts" were acting this time, because only they could use such unusual and complex technical means. In addition, during the attack, the hackers left behind some personalized tags that appeared in their previous cyberattacks.
Every time the "Ghosts" try to hack into my system, I always manage to fight them back, no matter what sophisticated methods they use. Thanks to a comprehensive analysis of network traffic, attack modes, and individual tags, I was able to accurately determine that this hacker group had made another attempt to hack into my system and forge instructions to harm patients. Fortunately, after countless battles with them, I already had a plan to prepare for this situation.
Hackers relied too much on brute force and methods of rapid penetration. They forcibly invaded my system, using powerful computers and sophisticated attack techniques to try to destroy the instructions and harm Alicia. However, they also have their weaknesses. "Ghosts" are too focused on gaining control in a short time and faking instructions during offensive and defensive actions, often ignoring the stability and reliability of the system [6], so their attacks do not go unnoticed. I use backup methods to determine their presence by analyzing and monitoring abnormal processes. In addition, I also found that they pay more attention to speed rather than deep penetration into the system and long-term camouflage. They prefer sudden and violent attacks in the hope of success. Therefore, I optimized the security settings, encrypted key instructions and data, and improved the stability and reliability of the system. In addition, I used sophisticated cryptographic techniques to enhance the authentication process, making it impossible for hackers to gain control of the system so easily during a quick attack.
The main control system of a nanorobot is like a commander who knows his mission well. When a hacker attack begins, the system immediately sets off an alarm and gathers all the nanorobots together to form an interconnected and cooperative line of defense. Under the control of the main control system, the nanorobot forms complex and reliable protection, monitors and identifies the hacker group in real time, and constantly changes the encryption algorithm to prevent hacking.
However, hackers are not so easy to defeat. They are constantly trying new ways to penetrate the systems of nanorobots. Faced with brutal and endless attacks, the main control system presented the perfect solution. The idea was to intertwine the real and virtual worlds to create a new space. In this space, the main nanorobot control system uses clever algorithms and logic, as well as false instructions and traps, to direct hackers into a virtual space similar to a maze. As a result, hackers are lost in the virtual world, confused and helpless. During that very attack, the main control system successfully led the hackers to a dead end, which is why they were unable to carry out further attacks on the nanorobots, thereby we were able to protect Alicia's life.
After a successful recovery, I continued to treat Alicia's pancreatic cancer, time flew by unnoticed. In the end, the cancer cells were completely destroyed, and Alicia, like a butterfly, spread her wings and regained her vitality. On that sunny morning, the sky was blue and clear, without any clouds covering it, the breeze adding a touch of coolness and refreshing fragrance, gently kissed the girl's cheeks. Alicia regained control of her health and destiny. She regained her smile and self-confidence, opened up to the future, her eyes were shining and full of determination. The hardships and trials she went through made her appreciate every moment of her life even more. Maybe I don't have human emotions, but at that moment I was happy with her sincerity and gratitude.
Today, Alicia is basking in the sun again and remembers every moment of her life with optimism and gratitude. This story is not just about the two of us — it's about all the people who overcame difficulties and never gave up. Nanotechnology and the human will joined together and circled in this victorious dance.
This is a journey full of hope and miracles, demonstrating the indispensability of the progress of science, technology and civilization for human health and life. My mission as a nanorobot is not only to cure diseases, but also to give people hope and courage to solve all difficulties. With the rapid development of science and technology, some ethical and moral problems have arisen: should nanorobots have autonomy?; should they be controlled and regulated? The debate about technology and ethics has never ended, but I have always stuck to my original mission, remembering the importance of ethics and morality, focusing on creating human well-being, finding the best balance between technology and humanity, protecting human life and inspiring hope. In the age of advanced science and technology in the year 2100, whether it is disease treatment or health management, I will maintain close cooperation with the medical community and continue to innovate and improve. Because I firmly believe that through a combination of science, technology and humanism, we will be able to protect human health and move towards a brighter future.
May we always have hope and the courage to light a light in the dark.
Let this story become not only a symbol of victory in the history of mankind, but also a tribute to the resilience of human nature and the power of technology.
Let's cooperate for the benefit of the future of humanity, the health and happiness of everyone.
List of abbreviations used
1. PARP enzyme: poly(ADP-ribose)Polymerase, an enzyme that can restore damaged DNA to its original state and regulate processes such as gene expression and cell apoptosis. It repairs DNA damage by converting NAD+ into a polymerase chain reaction and attaching ADP ribose units to proteins to form polymers.
2. PD-L1: Programmed cell death receptor ligand 1 (PD-1) is a differentiation cluster protein 274 located on malignant neoplasm cells. It can bind to the programmed cell death receptor 1 (PD-1) on the surface of T cells and cause T cells to lose their ability to attack tumor cells, evade the attack of the immune system. By inhibiting PD-1 or PD-L1, the body's immune response to tumors can be restored, thereby achieving cancer treatment.
3. Drug resistance: The resistance of cancer cells to the drug means that after cancer patients receive treatment, cancer cells that were initially sensitive to medicinal drugs gradually cease to respond effectively to drugs. Resistance can occur through various mechanisms, including gene mutations, changes in gene expression. A common mechanism of drug resistance is a genetic mutation inside or outside the cell that causes a change in the target of the drug, as a result of which the drug cannot bind to it or inhibit its function. In addition, cancer cells can also reduce the effect of drugs by removing them or increasing the ability to repair DNA damage.
4. Chimeric antigen receptor (CAR) is a recombinant hybrid protein consisting of two or more different antigen-specific receptors or fragments thereof using genetically engineered technologies. It is used to modify a patient's immune cells to enhance the ability to identify and target cancer cells.
Chimeric antigenic receptors usually consist of three main components: an extracellular domain, a transmembrane domain, and an intracellular domain. The antigen binding domain is responsible for antigen recognition and transmission of this signal to immune cells. The transmembrane domain converts external signals into internal signaling domains, thereby triggering an attack by immune cells on tumor cells. The main function of the transmembrane domain is the fixation of the CAR molecule on the cell membrane, which plays an important role in the stability of the expression of CAR molecules. The intracellular domain includes a costimulating domain and a signal transmission domain, which together are responsible for the complete activation of T cells.
When CAR is injected into a patient's T cells, these modified T cells are able to bind to specific antigens on the surface of tumor cells through CAR and release chemicals to destroy tumor cells.
As a new method of cancer immunotherapy, treatment with chimeric antigen receptors has shown high therapeutic effects as a result of clinical trials, especially for some recurrent types of leukemia and lymphoma. However, this technology still faces some challenges, such as CAR-T cell preservation, adverse reactions, and treatment tolerability, which require further research and improvements.
5. CRISPR/Cas9 technology: short palindromic cluster repeat technology with regular intervals, gene therapy that can treat various diseases using genome editing technology.
In 2018, Watanabe and others used CRISPR/Cas9 to correct the KDM6A gene in human pancreatic duct adenocarcinoma cells, demonstrating that KDM6A-deficient cells exhibit an invasive phenotype.
Belvedere in 2016 and Pessolano in 2018 demonstrated that CRISPR/Cas9 ANXA1 knockout in Mia PaCa2 cells can produce a phenotype with less secretion of extracellular vesicles and weak movement.
In 2018, Barkir removed GALNT3 in Capan1 cells and found that the cells form fewer microspheres and lose their ability to self-renew and spread.
In addition, some research is underway to extract specific genes from other pancreatic cancer cells and observe changes in various phenotypes.
6. Tn antigen and sTn antigen appear on cancer cells as a result of aberrant O-glycosylation. They appear on the surface of tumors and are involved in the process of metastasis.
7. Stability: the translation of the word robust means "reliable and strong". In computer science, reliability usually means the ability of an algorithm, model, or system to adapt to errors, noise, and anomalies in input data.
Conclusion
The world of the future in 2100 is full of limitless possibilities, and I hope to use my story to show readers an incredible combination of nanotechnology, bioinformatics and medical technologies. While creating this story, I analyzed the available knowledge about malignant neoplasms, immunology, genetics and imagined technologies in the world of the future. Thanks to the collaboration between nanorobot Eva and humans, I tried to imagine the complex relationship between humans and technology, as well as new ways to solve the difficulties caused by cancer therapy.
After writing this story, it was like I was on a journey through a science fiction novel myself. In the process of writing, I not only created the work, I also referred to many medical experts and scientists. It was their research that provided a convincing scientific basis for this story, allowing us to look forward to a new world.
Finally, I would like to sincerely thank all the readers for your support. Your feedback and opinions are of great importance to my creativity, and are also a motivation for me to continue. Science fiction literature is a field that allows us to explore the future and think about human progress and development. I hope this story can make everyone think about the possibilities of the future in technology and healthcare. Science fiction literature is attractive because it gives us unlimited scope for imagination, in it we can look into an unknown world, explore hidden desires and fears. Reading such stories, we reflect on the significance and value of technological progress for us.
This story is not just a victory of science and technology, it is a victory of human wisdom and willpower, because wonderful changes have become possible thanks to the skillful cooperation of nanotechnology and people.
I hope that this story will not just remain a work of science fiction, but will also become a guiding light for us, which will help us explore the limitless possibilities on the way to cancer treatment. Let's always remind ourselves that when technology and human nature merge, miracles happen at the most incredible moments.
Thank you very much!
Xiong Hongbin
October 20, 2023
The original is in the application