Scientific Harrovian Issue 4 (January 2023)

Scientific Harrovian

UNCOVERING THE SCIENTIFIC WORLD

WILL OUR FUTURE SURGEONS BE ROBOTS? NEW TREATMENTS FOR CANCER?

WHO WANTS TO LOOK YOUNG?

2022-2023 Issue viii - 1

Harrow International School Hong Kong

About the

Scientific Harrovian 2022

The Scientific Harrovian is the student run Science Department magazine, which provides a platform for students to showcase their research and writing talents, and for more experienced pupils to guide authors and to develop skills to help them prepare for life in higher education and beyond.

All images, unless otherwise specified, are obtained from Unsplash or Pexels Portrait photos credited to Dora Gan of Photography Society

a message from

Head of Biology

I would like to thank, and congratulate, all of the writers, editors and illustrators on the completion of this outstanding edition. You are each important cogs in the Scientific Harrovian machine, without each of you this edition simply would not have happened. The team has been run passionately by two exceptional students, Judy Sheng and Kevin Wu, who have motivated the team to produce well researched and written pieces across a range of subjects. The final piece was put together through the tireless efforts of Cyrus Tsui, our Chief Design Officer, resulting in an edition that is visually stunning. I hope everyone who picks up a copy of this Scientific Harrovian enjoys it too.

Editor-in-chief

I am delighted to welcome you to issue VIII-i of the Scientific Harrovian!

This year’s theme is ‘Uncovering the Scientific world’, with articles covering from spider silk to quantum computing. Each article is bound to give you a glimpse into unique realms of science, and I hope you enjoy them as much as I did!

Our team has made a great start to the year with countless hours of work put in by our writers, illustrators, editors, and members of the executive team. My greatest thanks go to all our contributors for their commitment and effort. It has been a huge pleasure to seeing the team grow and watching this publication come together as old and new members join us on another enthralling expedition into the Scientific World.

A special thanks to the members of our executive team, especially Cyrus Tsui (Chief Design Officer) and Grace Zhu (Deputy Design Officer) for putting together this amazing piece of work. And of course, to Kevin Wu, our Deputy Editor-in-Chief who led the team and helped coordinate this issue. None of this could have come together without each of their hard work.

I hope you enjoy!

a message from

Deputy Editor-in-chief

WELCOME!

As our life gradually recovers from the pandemic and returns to normality as a result of the vaccine, it is crucial for us to realise how the applications of sciences shape our world today. Hence, the theme of Edition VIII-i of the Scientific Harrovian is Science and life, focusing on the contemporary applications of science in our day-to-day life and its potential in the future.

With this issue being the time bearing such a great responsibility as the Head Editor in chief, I cannot express my gratitude enough towards Judy for not only trusting me but also for guiding me to make this issue possible. I would also like to thank Cyrus, the Chief design officer, for his expertise in designing and I’m truly amazed at how he managed to put everything together from scratch. Lastly, I would like to thank all the head editors, editors, and writers for dedicating your already precious time to attending weekly lunchtime meetings and contributing your part to the issue. This issue really wouldn’t be possible without any of you!

Enjoy!

Ms. McCrohan

Editor-in-Chief

Deputy Editor-in-Chief

Chief Design Officer

Deputy Chief Design Officer

Biology Head Editor

Chemistry Head Editor

Physics Head Editors

Judy Sheng

Year 13 Gellhorn

Kevin Wu

Year 12 Sun

Cyrus Tsui

Year 12 Peel

Grace Zhu Year 11 Gellhorn

Jenny Park Year 12 Wu

Adrian Lau

Year 12 Peel

Sky Lee Year 12 Shaftsbury

Emma Chua

Year 12 Gellhorn

Technology Head Editor

Emma Chua

Year 12 Gellhorn

writers

Jasmine Wong

Year 13 Keller

Sen Yi Mok

Year 11 Sha sbury

Gloria Kan

Year 12 Anderson

editors

Jack Wei Year 6 Banks

Tracy Zhang

Year 9 Wu

Davyn Kwok

Year 7 Darwin

Peony Sham

Year 12 Anderson

Cyrus Tsui Year 12 Peel

Ashlee Kwan

Year 11 Wu

Edward Wei Year 13 Peel

Clarence Chen Year 12 Sun

Emma Chua

Year 12 Gellhorn

illustrators

Tracy Zhang Year 9 Wu

Cindy Min Year 11 Gellhorn

Cyrus Tsui

Year 12 Peel

Kate Xiao

Year 12 Gellhorn

Daniel Kan

Year 11 Sha sbury

Audrey Lai

Year 12 Gellhorn

Bernice Ho

Year 9 Anderson

Sky Lee

Year 12 Sha sbury

Karen Li

Year 12 Gellhorn

Carol Yeung

Year 13 Keller

Bernice Ho

Year 9 Anderson

Callum Sanders

Year 12 Sha sbury

Rachel Pabaru

Year 12 Wu

Andrew Hung

Year 11 Churchill

Eileen Wu

Year 8 Nightingale

Sky Lee Year 12 Sha sbury

Zhaoping Sun Year 10 Churchill

Lara McWilliam

Year 13 Keller

Ivy Sham Year 9 Anderson

Andrea Lee

Year 11 Gellhorn

Valerie Ho Year 11 Anderson

Janus Guo

Year 6 Banks

Adrian Lau Year 12 Peel

Jenny Park Year 12 Wu

Grace Zhu

Year 11 Gellhorn

Ethan Lan

Year 9 Churchill

Aiden Lan

Year 6 Shackleton

Callum Sanders Year 12 Sha sbury

Sky Lee

Year 12 Sha sbury

CONTENTS

Physics and Technology

Will Our Future Surgeons be Robots? 12 Alphafold ----------------------------------------------20

The Fundamentals of Quantum Computing --------27

The Speed of Light and its Significance -------------35

Chemistry and Biology

Who Wants to Look Young? --------------------------46 New Treatments for Cancer? -------------------------51

How can sustainability be achieved through the arts of building design? ------------------------------------55

Medicinal Applications of Spider’s silk -------------61

The Power of Stem Cells ------------------------------69

PHYSICS and TECHNOLOGY

WILL OUR FUTURE SURGEONS BE ROBOTS?

By Daniel Kan

1. Introduction

Robotic surgery is the use of mechanical arms carrying surgical instruments that are controlled by a surgeon. Robotic surgery is generally used with minimally invasive surgeries, which use small incisions instead of the traditional open procedures.

2. The History of Robotic Surgery

The first application of robots in surgery was in 1985, when a Programmable Universal Machine for Assembly (PUMA 200) was used to perform a neurosurgical biopsy. [1] It was further adapted by The Robotics Center at Imperial College into the PROBOT [2], which was specifically designed to perform a transurethral resection of the prostate (TURP), a procedure that involves cutting away a section of the prostate. The PROBOT allows a surgeon to specify a volume of the prostate, which would automatically be cut by a rotating blade [3].

In 1992, the ROBODOC system was developed and became the first active robot system to achieve a formal FDA approval. This was used to improve the precision of hip replacement surgery. The ROBODOC system consists of a preoperative surgical planning workstation called ORTHODOC and a five-axis robotic arm to carry out the plan [4].

During the next decade, the field of robotic surgery underwent a paradigm shift in which research was more focused on the “master-slave” concept, where a surgeon would remotely control the movements of a robot from a distant workstation.

In 1989, a company called Computer Motion created a robotic platform called Automated Endoscopic System for Optimal Position (AESOP). This consisted of a robotic arm that held an endoscope which removed the need for an assistant to hold it. This had multiple benefits, such as not fatiginge during long procedures (unlike if an assistant was holding it), more stability, and less personnel required to be present in the operation.

Initially, the AESOP 1000 (approved in 1994) was controlled by pedals, but later the AESOP 2000 could be controlled using a voice control system. The final platform, the AESOP HR, also had voice control of other functions such as operating room lighting and movement of the operating table [5].

In 1998, the AESOP system was modified and relaunched as the ZEUS operating system, which had arms and surgical instruments that could

be remotely controlled by the surgeon. The ZEUS operating system had three arms: one was an AESOP camera system that was controlled by voice, the other two arms held surgical instruments that could be controlled using handles. In 2001, the first transatlantic surgery was carried out using the ZEUS system, where a surgeon from New York performed a cholecystectomy (removal of gallbladder) on a patient in France [6].

At the same time that the ZEUS system was being developed, another company called Intuitive Surgical was developing their own surgical robot. Their first prototype was called Lenny and had three arms: two for holding instruments and one for the camera. The second generation of robots was Mona, which was the first robotic surgical system to be used in human trials. However, in 1998, Intuitive surgical developed the da Vinci system, which would later become the most successful robotic surgery platform that is still used to this day. The first da Vinci robot had three arms: one that held the camera and the rest would hold instruments. These arms could rotate with seven degrees of freedom and two degrees of axial rotation – a significant selling point compared to other systems. The two companies Computer Motion and Intuitive Surgical then merged in 2003, discontinued the ZEUS system and worked together to improve the da Vinci system [7]. In 2000, the da Vinci system gained FDA approval for clinical use, and 2 years later a version with 4 arms was also approved. In 2006, the da Vinci S platform was released, with a 3D HD camera and an interactive touch screen display. In 2009, the da Vinci Si platform was released with dual console surgery, allowing two surgeons to operate at once. This optimised each surgeon’s potential as well as introduced a way to train non-expert surgeons. The Si system also had other improvements such as a better image system and real time fluorescence imaging. In 2014, the da Vinci Xi platform was created, as well as the da Vinci SP system, which had a single port and only required one incision.

3. How Does Robotic Surgery Work?

3.1. Robotic Surgery vs Minimally Invasive Surgery vs Open Surgery

Traditionally, open surgery requires the surgeon to make a large incision using a scalpel to view the necessary organs. Minimally invasive surgery (MIS) uses several small incisions and a laparoscope, which has a small camera attached to it, to allow the surgeon to examine the organs. MIS is generally less painful and has a faster recovery period compared to open surgery [8]. Robotic Surgery or Robot Assisted Surgery is generally associated with MIS and uses robotic arms that are controlled by the surgeon. The robotic arms hold a camera and surgical instruments. Robotic surgery has multiple advantages such as a greater range of motion and dexterity(ability to delicately manipulate with hands and fingers) for the surgeon [9]. It usually also has a faster recovery time.

3.2. How current Robotic Surgery works - The da Vinci system

The da Vinci system has 3 components: the surgeon console, the patient cart and the vision cart. These components follow the “master-slave” concept, where the surgeon console is the “master interface” and the patient cart holds the “slave manipulators” that hold the surgical instruments. The vision cart makes communication between components possible and supports the 3D HD vision system [10].

The surgeon console allows the surgeon to see inside the patient and control the manipulators. The stereo viewer gives the surgeon a 3D-HD view which immerses the surgeon in the surgical field, something that was lost when doing traditional minimally invasive surgery. The two master controllers allow the surgeon to control the instruments and endoscope. The surgeon can use their hands to move the master controllers, and the actions will be replicated by the manipulators. The manipulators are designed to allow a natural range of motion, dexterity and ergonomic comfort (when using and holding) [11]. Through these controllers, the surgeon’s hand tremors can be filtered out from the electronic signal or scaled down. The surgeon console also has left side and right side pods, which contain controls such as ergonomic controls, the power button, and an emergency stop button [12]. The surgeon console also has a footswitch panel which allows the surgeon to control different things using their feet without having to remove their head from the 3D viewer.

The Patient cart is the operative component of the system and has four arms that hold all the instruments and endoscope. During the operation, instruments and endoscopes are swapped by the assistant surgeon.

The Vision cart holds electronic equipment for visualisation. It includes a light source to illuminate the surgical site, soft ware processing units to process the video images and send it to the 3D viewer and touchscreen.

3.3. Visualisation

The da Vinci Surgical system uses endoscopes to allow the surgeon to visualise the area they are operating on. These endoscopes transmit white-light to form images that only show the visible surfaces of the organs [13]. Recently, there have been further innovations with other techniques such as the Firefly Fluorescence imaging. This works by injecting a fluorescent agent into the bloodstream which will emit light when excited. This is then excited using a corresponding excitation light source and the fluorescence can be detected using a specific detector. The most widely used fluorescent agent is indocyanine green (ICG), which rapidly binds to plasma proteins in the blood. When the ICG fluoresces, the image detected can be combined with the white light image to allow the surgeon to see vasculature and tissue perfusion. One way that ICG is removed from the blood is by secreting it into bile at the liver. This can allow the surgeon to visualise the structures of the bile duct.

There are many other techniques that can be used for visualisation. Dynamic view expansion or mosaicing can offer a wider field of view [14]. Narrow Band Imaging uses specific filters to modify white light images to increase contrast which allows surgeons to more clearly view a certain part of the tissue [15]. Tomographic imaging can be used before or during surgery which uses penetrating waves to provide cross sectional images beyond the surface tissue.

3.4. The Surgical Instruments

The surgical instruments used by the da Vinci system have an articulated wrist mechanism called EndoWrist which allows it to have more dexterity and a greater range of motion [10]. EndoWrist instruments include endoscopic dissectors, scissors, scalpels, forceps, needle holders, needle drivers, retractors, bipolar and monopolar energy instruments, suction irrigation instruments, staplers, and more [16].

The staplers are used in transection and resection by placing multiple rows of staples then transecting the tissue with a knife blade, cleanly cutting the tissue without any bleeding [13]. The stapler is controlled by the foot pedals at the surgeon console.

There are also instruments that use energy. These are split into monopolar and bipolar instruments. Monopolar is when the current passes from the electrode to the target tissue then to a return pad and back to the generator to complete the circuit. Bipolar is when the current passes from one side of the instrument to the other side of the instrument, and only the tissue between the instrument is affected.

There are three monopolar instruments used in the da Vinci system: the hook, the scissors, and the spatula [16]. The most common monopolar instrument is the hook, which allows the surgeon to dissect and apply energy to a certain area. The scissors allow the surgeon to precisely dissect tissue in restricted spaces. The spatula is used for desiccation (drying out of cells) over a wide area [17].

Several bipolar instruments are used in the da Vinci system. The bipolar grasper is used to grasp and retract tissue, and can also be used for hemostasis of small blood vessels. The bipolar forceps can also be used for hemostasis of small vessels, as well as being used to cut, although this is rarely used [17]. The Vessel sealer extend and Vessel sealer can seal and cut vessels. They do this by precisely applying pressure and energy to control the temperature, causing soft tissue proteins to denature and melting the inside walls of the vessel together. Once the vessel is sealed, a mechanical knife can be used to cut through the vessel. The vessel sealer can also be used for dissection, which decreases operative time by removing the need to change instruments.

SynchroSeal is another instrument that can also seal vessels. It is more efficient than vessel sealer since it only requires a single pedal press to seal and cut as opposed to two pedal presses. However, Vessel sealer extend can seal and cut vessels up to 7 mm in diameter, whilst SynchroSeal can only seal and cut vessels up to 5mm in diameter.

4. Current Appliations of Robotic Surgery

Currently, robot assisted surgery is used across a wide range of surgical specialties. Whilst robotic surgery is most commonly performed in urological, gynaecological and gastrointestinal surgery [18], robotic surgery has also seen use in many other specialties.

4.1. Urological surgery

Due to the depth of the pelvis and small size of the structures [19], prostatectomy was one of the first surgical operations to widely adopt robotic surgery. This allows surgeons to more easily guide the instruments to the required location (eg. prostate, kidneys), which is more advantageous when compared to open surgery or traditional laparoscopic techniques. As well as prostatectomy, robotic surgery has also been used in nephrectomies and adrenalectomies. Overall, robotic surgery has been widely adopted for urologic surgery, especially for performing prostatectomies.

4.2. Gynaecological surgery

Robotic surgery has been used to perform many operations in gynaecology. It is estimated that over 60% of hysterectomy procedures (removal of the uterus) were done robotically [21]. Robotic surgery has also been used in myomectomy (removal of uterine fibroids whilst preserving the uterus), tubal reanastomosis, and pelvic and paraaortic lymph node dissection [21].

4.3. Application in gastrointestinal surgery

The increased quality of the images produced by the endoscope and increased precision of its instrument is important in the treatment of gastrointestinal cancer [22]. This includes removal of cancer in organs such as the stomach, liver, gallbladder, small bladder, adrenal, colon, and others [19].

4.4. Other surgical fields

Robotic surgery has also seen use in other surgical fields. In otolaryngological (head and neck) surgery, robotic surgery allows for smaller incisions whilst still allowing the surgeon to have clear visualisation and dexterity. In neurosurgery, robotic surgery allows surgeons to surpass the limits of human dexterity on a microscopic scale, although it does have its limitations such as speed and lack of sense of touch. In cardiothoracic surgery, robotic surgery has been used for mitral valve surgery, repairing atrial septal defect, anastomosis on an arrested heart, anastomosis on a beating heart, and more [19].

5. Future Applications of Robotic Surgery

5.1. Telerobotic Surgery

Telerobotic surgery, also known as remote surgery, is robotic surgery where the surgeon is in a distant place and communicates through a wireless network. This was initially explored by NASA who wanted a type of surgery that could be performed in space, but it can also be applied on earth so patients do not have to travel long distances [23]. Telerobotic surgery allows surgeons from around the world to perform surgery in rural areas or places with surgeon shortage. It can even allow for collaboration of multiple surgeons which can be used to enhance care, as well as for training [24].

However, latency time (delay) has been a significant drawback, as too much time delay can lead to inaccuracies. Developments in 5G technology can be useful for reducing this. There can also be problems with cyber security, cost, and legal issues across country borders [24].

Despite some of these issues, in 2019 researchers in China successfully performed 12 telerobotic spinal surgeries using 5G, all of which were successful. In all of these, the master surgeon was in a different province to the patient. The researchers concluded that using 5G telerobotic surgery was “accurate, safe, and reliable” [25].

5.2. Nanorobotic surgery

Nanorobots are tiny robots that can move around the patient’s entire body through the bloodstream (including capillaries) to access different cells. This can be used for highly precise surgery down to the cellular level, as well as accessing hard to reach places. Nanorobots can take many forms, such as nanodrillers, micro-grippers, micro bullets, and more [26]. Aside from surgery, nanorobots can also be used for targeted drug delivery, diagnosis, detection, biopsies, imaging, 3D printing, and more [27]. However, nanorobotics is just beginning and there still are many challenges that need to be overcome.

7. Bibiliography

[1] Kwoh, Y.S., et al. “A Robot with Improved Absolute Positioning Accuracy for CT Guided Stereotactic Brain Surgery.” IEEE Transactions on Biomedical Engineering, vol. 35, no. 2, 1988, pp. 153–160., https://doi.org/10.1109/10.1354.

[2] “Probot.” Imperial College London, www.imperial.ac.uk/mechatronics-in-medicine/research/probot/.

[3] “The Method of Cutting the Prostate with the Robot.” Imperial College London, www.imperial.ac.uk/mechatronics-in-medicine/research/probot/cutting/.

[4] Bargar, William L., et al. “Primary and Revision Total Hip Replacement Using the Robodoc?? System.” Clinical Orthopaedics and Related Research, vol. 354, 1998, pp. 82–91., doi:10.1097/00003086-199809000-00011.

[5] MORRELL, ANDRE LUIZ, et al. “The History of Robotic Surgery and Its Evolution: When Illusion Becomes Reality.” Revista Do Colégio Brasileiro De Cirurgiões, vol. 48, 2021, doi:10.1590/0100-6991e-20202798.

[6] Marescaux, Jacques, et al. “Transatlantic Robot-Assisted Telesurgery.” Nature, vol. 413, no. 6854, 2001, pp. 379–380., doi:10.1038/35096636.

[7] Lane, Tim. “A Short History of Robotic Surgery.” The Annals of The Royal College of Surgeons of England, vol. 100, no. 6_sup, 2018, pp. 5–7., doi:10.1308/rcsann.supp1.5.

[8] “Open Surgery vs Laparoscopic Surgery: Which Is the Best Procedure?” Far North Surgery, www.farnorthsurgery.com/blog/open-surgery-vs-laparoscopic-surgery.

[9] “What Is Robotic Surgery?” UCLA Health System, www.uclahealth.org/medical-services/robotic-surgery/what-robotic-surgery.

[10] “About Da Vinci Systems.” Da Vinci Surgery | Da Vinci Surgical System | Robotic Technology, www.davincisurgery.com/da-vinci-systems/about-davinci-systems.

In the future, it is possible that robots will be able to perform surgeries autonomously without the control of a human surgeon. To do this, the robot will have to be able to interpret visual and physical data, then decide what to do and carry it out [28]. It will also need to be able to adapt to different situations in real time. To achieve this, various machine learning algorithms will need to be used for receiving and interpreting data, as well as being “taught” how to actually perform the surgery.

Although current robotic surgeries are still done by humans, recently, a robot successfully performed an intestinal anastomosis on a pig without any direct human assistance using the Smart Tissue Autonomous Robot (STAR) [29].

6. Future Applications of Robotic Surgery

In conclusion, robotic surgery is a type of minimally invasive surgery that uses robotic arms to perform surgery. Currently, it uses the “master-slave” concept where a surgeon directly controls robotic manipulators that hold surgical instruments and an endoscope. There are many benefits of robotic surgery including more dexterity, better visualisation, and faster recovery times. However, robotic surgery is very expensive, which is why it hasn’t been as widely adopted as it could be. Fields where robotic surgery is used the most are: urological surgery, gynaecological surgery, and gastrointestinal surgery. In the future, it could be used for telerobotic surgery where the surgeon controls the robot remotely, nanorobotic surgery where nanorobots move through the bloodstream, or autonomous surgery where the robot performs without any human assistance.

[11] Mishra, R.K., System Components - World Laparoscopy Hospital. www.laparoscopyhospital.com/Book/Ch-03.pdf.

[12] Intuitive Surgical, da Vinci Si surgical system User Manual, Intuitive Surgical

[13] Azizian, Mahdi, et al. “The Da Vinci Surgical System.” The Encyclopedia of Medical Robotics, 2018, pp. 3–28., doi:10.1142/9789813232266_0001.

[14] Lerotic, Mirna, et al. “Dynamic View Expansion for Enhanced Navigation in Natural Orifice Transluminal Endoscopic Surgery.” Medical Image Computing and Computer-Assisted Intervention – MICCAI 2008, 2008, pp. 467–475., doi:10.1007/978-3-540-85990-1_56.

[15] Barbeiro, Sandra, et al. “Narrow-Band Imaging: Clinical Application in Gastrointestinal Endoscopy.” GE - Portuguese Journal of Gastroenterology, vol. 26, no. 1, 2018, pp. 40–53., doi:10.1159/000487470.

[16] Da Vinci X & Da Vinci XI Instrument & Accessory Catalogue - Intuitive.com. Intuitive Surgical, Mar. 2022, www.intuitive.com/en-gb/-/media/ISI/ Intuitive/Pdf/da-vinci-x-xi-instrument-accessory-catalogue-1075017.pdf.

[17] Wikiel, Krzysztof J., et al. “Energy in Robotic Surgery.” Annals of Laparoscopic and Endoscopic Surgery, vol. 6, 2021, pp. 9–9., doi:10.21037/ ales.2020.03.06.

[18] Anderson, Jamie E., et al. “The First National Examination of Outcomes and Trends in Robotic Surgery in the United States.” Journal of the American College of Surgeons, vol. 215, no. 1, July 2012, pp. 107–114., doi:10.1016/j.jamcollsurg.2012.02.005.

[19] Shah, Jay, et al. “The History of Robotics in Surgical Specialties.” American Journal of Robotic Surgery, vol. 1, no. 1, 2014, pp. 12–20., doi:10.1166/ ajrs.2014.1006.

[20] Bharathan, Rasiah, et al. “Operating Room of the Future.” Best Practice & Research Clinical Obstetrics & Gynaecology, vol. 27, no. 3, 21 Dec. 2012, pp. 311–322., doi:10.1016/j.bpobgyn.2012.11.003.

[21] Leddy, Laura, et al. “Robotic Surgery: Applications and Cost Effectiveness.” Open Access Surgery, 2 Sept. 2010, p. 99., doi:10.2147/oas.s10422.

[22] Ohuchida, Kenoki. “Robotic Surgery in Gastrointestinal Surgery.” Cyborg and Bionic Systems, vol. 2020, 2020, pp. 1–7., doi:10.34133/2020/9724807.

[23] Mohan, Anmol et al. “Telesurgery and Robotics: An Improved and Efficient Era.” Cureus vol. 13,3 e14124. 26 Mar. 2021, doi:10.7759/cureus.14124

[24] Choi, Paul J, et al. “Telesurgery: Past, Present, and Future.” Cureus, 2018, doi:10.7759/cureus.2716.

[25] Tian, Wei et al. “Telerobotic Spinal Surgery Based on 5G Network: The First 12 Cases.” Neurospine vol. 17,1 (2020): 114-120. doi:10.14245/ ns.1938454.227

[26] Li, Jinxing et al. “Micro/Nanorobots for Biomedicine: Delivery, Surgery, Sensing, and Detoxification.” Science robotics vol. 2,4 (2017): eaam6431. doi:10.1126/scirobotics.aam6431

[27] Eggleton, Benjamin. “Nanorobotic Surgery.” Nanorobotic Surgery, The University of Sydney, www.sydney.edu.au/nano/our-research/research-programs/nanorobotic-surgery.html.

[28] Panesar, Sandip, et al. “Artificial Intelligence and the Future of Surgical Robotics.” Annals of Surgery, vol. 270, no. 2, Aug. 2019, pp. 223–226., doi:10.1097/sla.0000000000003262.

[29] Saeidi, H., et al. “Autonomous Robotic Laparoscopic Surgery for Intestinal Anastomosis.” Science Robotics, vol. 7, no. 62, 26 Jan. 2022, doi:10.1126/ scirobotics.abj2908.

Figure 1: https://www.researchgate.net/figure/Puma-200-the-first-robot-used-for-assisting-human-neurosurgery-1985-12_fig2_290495998

Figure 2: https://www.researchgate.net/figure/ZEUS-robotic-system-first-robotic-system-to-combine-instrument-and-camera-control_fig3_51437277

Figure 3: http://www.rsalinas.com/davinci-si-1-1

Figure 4: https://www.advancedurologyinstitute.com/da-vinci-surgical-system/

Figure 5: https://www.ourmidland.com/news/article/Firefly-glow-improves-visibility-in-surgery-6946851.php

Figure 6: https://entokey.com/the-da-vinci-system-technology-and-surgical-analysis/

Figure 7 and 8: https://www.intuitive.com/

5.3. Autonomous robots

1. Introduction

Proteins are everywhere, from specifically shaped enzymes that catalyse metabolic processes, to the fibrous, connective tissue made of collagen present in just about every organ in the body, to the body’s chemical messengers, hormones, that are secreted from exocrine glands and travel in the bloodstream. They play an irreplaceably crucial role in our daily lives, impacting our appearance, our actions, and most importantly, our survival!

Hence, AlphaFold is an extremely useful AI, as it can predict how chains of amino acids can fold into complex 3D structures, namely secondary, tertiary and quaternary, as protein functions are highly reliant on their shapes. However, before we go into the specifics of how AlphaFold works, we should understand why it is necessary first.

ALPHAFOLD

What Is It and Does it Really Solve the Protein Folding Problem?

By Gloria Kan

Traditionally, X-ray crystallography has always been the principal technique used to determine the complex 3D structure of proteins, especially for small, soluble proteins [6]. It goes through the following stages:

1. Crystallisation; this is when a pure, highly concentrated sample of protein is crystallised. pH, concentration, temperature and additive inclusion are controlled to optimise the yield and quality of protein crystals suitable to determine the structure of a protein.

2. A single X ray beam is generated by accelerating electrons caused by an electron striking a copper anode, and it is passed through slits that are approximately 0.1-0.3 mm wide, which causes diffraction (the spreading out of waves) [2].

3. A CCD (charge-coupled device) collects the X-ray diffraction images; it is generally preferred over conventional X-ray film or imaging plates due to its high level of sensitivity and the fact that the images can be collected rapidly (in a matter of seconds).

4. Resolution is calculated; it is important for it to be 1.5-3 Å (1Å is 1x10^−10 m), ensuring all amino acid side chains can be identified. (For reference, a carbon bond is approximately 1.5 Å) [2].

5. Data can then be collected for an electron density map, and analysed for a final structure.

(Figure 1: the structure of a potential plant disease resistance protein [14])

Another rapidly advancing procedure is single-particle cryo-electron microscopy (cryo-EM) [1], a method that is most prominent in identifying larger protein structures. Its procedures are [3]:

1. Apply a pure protein sample to a grid with small holes in its film.

2. Put the grid into a cryogen (a gas at a very low temperature; an example may be liquid nitrogen) to flash-freeze and trap particles in a thin film of vitreous ice. This is to protect the sample from any damage caused by radiation.

3. In the transmission electron microscope, a low electron dose is used to reduce damage done to the sample. As signals can be weak, many particles from the sample are analysed by a computer algorithm, to form one image of the particle; this is known as particle averaging.

4. Many 2D views of the protein obtained from different angles are processed to align images and merge data for a 3D map. Instead of having to convert electrons to photons, direct detectors can now detect electrons directly, allowing images to be recorded like a movie, resulting in a higher resolution (as motion correction can be used to reduce radiation drift) .

5. The main protein sequences are then fitted into a 3D map for a 3D model of the protein.

There is also NMR (Nuclear Magnetic Resonance) spectroscopy [4]. Its method is as follows:

1. Put the sample into a strong magnetic field —the stronger it is, the more detailed molecules can be studied, causing some atomic nuclei to act as small magnets.

2. When a range of frequencies is applied to it, the nuclei resonate at specific frequencies.

3. These frequencies of the nuclei are measured and analysed on a spectrum where intensity increases with larger resonating nuclei.

4. The value of the frequency gives information about the relative positions of atoms.

5. By examining the cross peaks of intensity, scientists can determine the 3D structures of proteins.

(Figure 4: example of a one-dimensional NMR spectrum of rubredoxin, a small protein [16])

(Figure 5: NMR is nuclear magnetic resonance spectroscopy, 3DEM is 3D electron microscopy and Mx is macromolecular crystallography (essentially cryo-EM) [5])

(Figure 2: the stages of X-ray crystallography [2])

(Figure 3: the process of cryo-electron microscopy [15])

Unfortunately, these methods can be very time-consuming and expensive, as it can take anytime from a few months to years of painstaking effort for one protein structure to be identified by a research lab. Before AlphaFold, it took over 50 years of arduous experimental efforts for scientists to identify the structures of approximately 100,000 proteins (around 50,000 being human protein structures). However, despite this impressive number, it is only about 17% of the human proteins, and many structures only cover a fragment of the sequence [8]. Thus, AlphaFold is a great advancement in the realm of biology, as it can predict protein structures quickly with a fairly high level of confidence.

2. The history of AlphaFold (A7D and CASP13)

It all started when DeepMind, the developer of AlphaFold (previously known as A7D), entered CASP13 (the critical assessment of protein structure prediction), a prestigious competition that has been running since 1994 [7]. For fairness, they use a system of blind testing, a method of testing the entrants’ modelling systems with the structures (of recently discovered proteins) that haven’t been input into the protein data bank yet.

In CASP13, DeepMind’s model structure, A7D, secured them the top place in the competition. They used three different free-modelling methods; a GDT-net, a gradient descent to predict backbone structure, and a distance potential fragment assembly, with the gradient descent method achieving the highest scores and high accuracy structures (GDT_TS, a measure of the similarity of a model and a predicted structure scores of 70 or higher out of a 100 being predicted in) being predicted for 11/43 GDT-net proteins [10].

Its overall design combined predictions of several neural networks that estimated the distances between the carbon atoms of pairs of residues, since residues may have been positioned closely together even if they weren’t close in the sequence of amino acids. As a result, a contact map with data about distances and angles for each residue could be used to predict a 3D structure.

However, with A7D, overfitting was present; interactions between residues were over accounted for, and, as a result, models were believed to have more secondary structures when it wasn’t necessarily true (i.e. the AI believed that the protein had more alpha helices and beta pleated sheets than interactions between tertiary or quaternary structures).

restraints, violations of any constraints (especially peptide bond geometry, as it is less controlled in the structure module) can be resolved with coordinate restrained gradient descent.

As for the results achieved in CASP14, AlphaFold 2 received an overall z-score (indicating similarity between two protein models) of 244.0217, while the next best group scored 90.8241. Moreover, AlphaFold managed the best prediction out of all participants for 88 out of 97 of targets, with levels of accuracy equivalent to experimental x-ray crystallography.

Since CASP13, AlphaFold has gone through drastic improvements. First, the AlphaFold network can now directly predict the 3D coordinates of a given protein using the primary amino acid sequence as inputs [9]. It starts by employing Multiple Sequence Alignments (MSAs) with different regions weighted by importance (attention) through repeated layers of a novel neural network block (also known as Evoformer) [11]. Then, in the trunk, it extracts information about the relationships between the protein sequence and template structure, producing a Seq N x Res N array (where Seq N is the number of sequences and Res N is the number of residues); residues are also known as unique R groups in an amino acid giving it its properties. Furthermore, in the trunk, there are regular updates about the relationship between the sequence-residue and residue-residue edges of a graph in order to achieve consistency and fit the constraints.

In the head, the structure module treats the protein as if it is a residue gas moving around the network to generate the protein’s 3D structure. Initially, rotations are set to identity and all positions are at the origin, but a protein structure is swiftly developed. And, unlike A7D, end-to-end folding is used instead of gradient descent, and the 3D transformer directly operates on a rigid 3D backbone using pair representation and the original sequence row from the MSA to build the side chains.

After that, there is the refinement step, which ‘refines’, or improves the accuracy and stereochemical qualities of the protein, and a step known as relaxation. As the result isn’t guaranteed to obey all stereochemical

4. Limitations

However, AlphaFold cannot perfectly predict protein structures. Some predictions made by AlphaFold fail to reach a high level of accuracy in CASP14. T1047s1-D1, for example, only managed a median accuracy value of 50.47 (out of 5 models) with a long beta sheet at a completely incorrect angle from the domain (the rest of the structure), and this is thought to be due to it having “a very high oligomerization state (quaternary structure)” and a “lack of other intra-domain structure” [12]. Thus, it can be discerned that it is very difficult for AlphaFold to predict proteins consisting of one or more polypeptides.

Furthermore, AlphaFold can only predict backbone and side chain structure for a particular conformational state (i.e. active or inactive), so, at times, the predicted conformation isn’t necessarily the conformation that would be found in an experiment. An example would be Model 1 of T1024, where the wrong state was thought to be predicted, resulting in a low accuracy prediction. Areas that are “intrinsically disordered or unstructured in isolation” will also predict a “ribbon-like appearance”, leading to low confidence as its structure in different conformations is not certain.

Finally, AlphaFold only focuses on amino acid sequences, so it doesn’t take into account any other ions, DNA, RNA, ligands, metals, or cofactors. For instance, AlphaFold would not have been able to accurately predict the structure of haemoglobin, as it consists of haem groups. In addition, PTMs (post translational modifications) that may alter the structure of a protein dramatically aren’t considered, and the AI cannot predict the effect of mutations either.

3. CASP14 and AlphaFold

(Figure 6: How AlphaFold 2 works [13])

5. Conclusion

Ultimately, AlphaFold is undoubtedly a revolutionary computational method that can accelerate the process of discovering proteins exponentially, especially since 98.5% of full chain human proteins can be predicted by AlphaFold [8]. While it cannot replace existing experimental methods or solve the protein folding problem, it can act as a guide for scientists to use, providing them with hypotheses for the structure of a protein.

6. Bibliography

[1] Thompson, Michael C., et al. “Advances in Methods for Atomic Resolution Macromolecular Structure Determination.” F1000Research, F1000Research, 2 July 2020.https://f1000research.com/articles/9-667/v1

[2] Smyth, M S, and J H Martin. “X Ray Crystallography.” Molecular Pathology : MP, U.S. National Library of Medicine, Feb. 2000. https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC1186895/

[3] Doerr, Allison. “Single-Particle Cryo-Electron Microscopy.” Nature News, Nature Publishing Group, 30 Dec. 2015. https://www.nature.com/ articles/nmeth.3700

[4] Zinkel, Brian. “What Is NMR Spectroscopy and How Does It Work?” Nanalysis, Nanalysis, 28 June 2019.https://www.nanalysis.com/ nmready-blog/2019/6/26/what-is-nmr-spectrography-and-how-does-it-work#:~:text=How%20Does%20NMR%20Actually%20Work,at%20 their%20own%20specific%20frequencies

[5] “Protein Data Bank: the Single Global Archive for 3D Macromolecular Structure Data.” Academic.oup.com, 8 Jan. 2019. https://academic. oup.com/nar/article/47/D1/D520/5144142

[6] Jaskolski, Mariusz, et al. A Brief History of Macromolecular Crystallography, Illustrated by a ... 3 Apr. 2014. https://febs.onlinelibrary.wiley. com/doi/10.1111/febs.12796

[7] Jumper, John, et al. “Highly Accurate Protein Structure Prediction with Alphafold.” Nature News, Nature Publishing Group, 15 July 2021. https://www.nature.com/articles/s41586-021-03819-2

[8] Tunyasuvunakool, Kathryn, et al. “Highly Accurate Protein Structure Prediction for the Human Proteome.” Nature News, Nature Publishing Group, 22 July 2021.https://www.nature.com/articles/s41586-021-03828-1

[9] Skolnick, Jeffrey, et al. “Alphafold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure, and Function.” Journal of Chemical Information and Modeling, U.S. National Library of Medicine, 25 Oct. 2021. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC8592092/

[10] Senior, Andrew W., et al. Protein Structure Prediction Using Multiple Deep ... - Wiley Online Library. 10 Oct. 2019. https://onlinelibrary. wiley.com/doi/full/10.1002/prot.25834

[11] Skolnick, Jeffrey, et al. “Alphafold 2: Why It Works and Its Implications for Understanding the Relationships of Protein Sequence, Structure, and Function.” Journal of Chemical Information and Modeling, U.S. National Library of Medicine, 25 Oct. 2021. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC8592092/

[12] Jumper, John, et al. Applying and Improving Alphafold at CASP14 - Wiley Online Library. 2 Oct. 2021. https://onlinelibrary.wiley.com/ doi/full/10.1002/prot.26257

[13] Jumper, John, et al. Alphafold 2 - Mimuw.edu.pl. 1 Dec. 2020https://www.mimuw.edu.pl/~lukaskoz/teaching/adp/lectures/lecture6/2020_12_01_TS_predictor_AlphaFold2.pdf

[14] Database, AlphaFold Protein Structure. “Alphafold FAQs.” Alphafold Protein Structure Database. https://alphafold.ebi.ac.uk/

[15] “Cryo-Electron Microscopy: Small Electrons to Visualize Large Molecules.” Università Vita-Salute San Raffaele, 16 June 2020, https://www. unisr.it/en/news/2020/6/criomicroscopia-elettronica-piccoli-elettroni-per-visualizzare-grandi-molecole.

[16] Example of a One-Dimensional NMR Spectrum of a Small Protein ... https://www.researchgate.net/figure/Example-of-a-one-dimensionalNMR-spectrum-of-a-small-protein-Rubredoxin-with_fig2_224830551.

Yi Mok

Estimated to be a one trillion dollar industry, quantum computing is a revolutionary new field which would reach market sizes close to the global tourism industry [1,2]. Instead of standard bits that store memory in supercomputers, quantum computers use qubits (also known as quantum bits) which can represent a huge number of states simultaneously [3]. Through the uses of qubits and quantum physics, quantum computing has been proven to be able to solve BQP (Bounded-error Quantum Polynomial) problems in the subset of NP (Nondeterministic polynomial) problems that typical supercomputers can never feasibly be able to solve [4,5]. This is also referred to as quantum supremacy. This would allow massive developments in quantum chemistry like ab initio calculations, encryption, weather forecasting, and stock market analysis [2,6].

Quantum supremacy has been first claimed to be proven in October 2019 by the 54-qubit processor Google “Sycamore” despite comments by IBM researchers that the supercomputer “Summit” could achieve similar results in 2.5 days [7,8]. Quantum supremacy was later demonstrated by China’s 113-qubit “Jiuzhang 2.0” in 2020 (1024 times faster than supercomputers) and currently, IBM’s 127-qubit “Eagle” developed in late 2021 is the fastest quantum computer as of 10 Nov 2022 [7,8].

2. Superposition

The reason why quantum computers are so much more powerful than regular supercomputers is because of two phenomena of quantum physics: superposition and entanglement [9]. Unlike regular bits that can only store ‘0’s or ‘1’s, qubits, a two-level quantum system can store a linear combination of basis states which can act like axes on a plane [10]. For qubits, the basis states are the ket-vectors : | 0 > and | 1 >.

Similar to vectors, the superposition of qubits can be thought of as a combination of different magnitudes of the basis states or adding vectors together [10]. For example, a superposition of a qubit can be < | 0 >

+ <√3 | 1 >. The left- hand side (< | or < | ) is known as the bra-vectors and combined with the right ket-vectors ( 0 > or 1 > ) make up the bra-ket notation. It is key to note that this superposition is simply one of an infinite number of potential combinations of different magnitudes of vectors, but not multiple states at once [10]. The special property of superposition allows qubits to represent over 2n potential states at the same time with only n qubits [9].

To represent the superposition of qubits, we can use 2 constants α and β which are complex numbers (for expressing wave functions of subatomic particles) where | > = | 0> + | 1> and |α|2 + |β|2 = 1 [11]. Despite having four components (real and imaginary parts of α and β), the 3D Bloch sphere can be used to visualise the points after simplifying the equation into: where (phi) is the imaginary part of β ( ) - the imaginary part of ( ) which represents the angle between the x-axis and where the point (psi) touches the XY plane whilst (theta) represents the angle from the z-axis and the line to the point from the origin [11]. Using the above equation, we can deduce that an arrow pointing up along the z-axis means that the qubit will always collapse into | 0 > and vice versa.

However, when qubits are measured, they collapse into one of their eigenstates which is either | 0 > or | 1 > based on probabilities in the bra-ket notation.

Given the above example, < | 0 > + < | 1 >, to find the probability of the qubit that will converge into | 0 >, first square this expanded expression < 0 | 0 > + < 0 | 1 > which results in this expression < 0 | 0 > + < 0 | 1 >. It is important to note that < 0 | 0 > and < 1 | 1 > is equivalent to 1 as the bra-vector matches the ket-vector whilst the bra-vectors < 1 | 0 > and < 0 | 1 > is 0 as the two vectors are not equivalent [10]. Therefore, we get x 1 + x 0 which is equivalent to or 25%. On the other hand, you can find the probability that the qubit will collapse into | 1 > using the same method which results in 75% or you can subtract the probability of collapsing into the eigenstate | 0 > from 1 which would be 1 - in this case and leads to the same result: 75%.

Another property of qubits is entanglement. Entanglement, otherwise known as “spooky action at a distance” by Einstein, refers to the fact that a pair of particles can share a distinct feature where the measurement of the first particle in the pair is perfectly correlated with the second particle in the pair [9, 13]. For example, if two subatomic particles (Particle A and Particle B) are entangled and the total ‘spin’ of the system is 0, if Particle A is measured to be counterclockwise, Particle B is guaranteed to have a measurement that is clockwise instantaneously after Particle A’s measurement no matter how far the particles are from each other [13]. However, communication using these particles is impossible as it is impossible to determine their final state before measurement and there is no way to copy any of the particles [9, 37]. This is due to the no-cloning theorem, which means that it is impossible to abstract information about the two coefficients of the superposition [37]. Entanglement can help speed up quantum computers by using the determined properties of other entangled qubits and is shown to be necessary for quantum supremacy [14].

Quantum gates are used in quantum computing to make necessary calculations and can be represented by matrices. They can alter the states of the qubit when the gates are applied to the qubits and are always reversible [15]. Unlike regular logic gates like AND or NOT gates, the input and outputs of these quantum gates can be in superposition [16]. Here are a few examples of single qubit quantum gates:

The Identity Gate, or the ‘I’ Gate, acts as a do-nothing operation and does not change anything about the qubit.

The Hadamard Gate essentially changes the state of the qubit so it is in a superposition such that it has an equal probability of converging to either the | 0 > or | 1 > eigenstate when observed [15]. It can also be described as a rotation around the Bloch sphere vector (1, 0, 1) [17].

3. Entanglement

4. Quantum Gates

Figure 1 shows a Bloch Sphere as described above [12].

Figure 2 shows the Identity Matrix or the Identity Gate [17].

Figure 3 shows the Hadamard Gate Matrix [17].

Pauli Gates, flips the qubit in the X, Y or Z axis depending on the specific Pauli Gate along their position on the Bloch Sphere. These gates are also known as X, Y or Z Gates. For example, after applying the X Pauli Gate (equivalent to the NOT gate in classical computers), the Z position is inverted whilst the X and Z positions are inverted after applying the Y Pauli Gate, and only the X position is inverted after applying the Z Pauli Gate [15, 17].

Through the manipulation of quantum gates and using the properties of qubits, quantum computers are able to do complex calculations. However, since a qubit collapses to one of the eigenstates

| 0 > or | 1 > based on probability, these calculations have to be repeated several times to ensure that the output matches the result that should be obtained [16].

5. Qubits

ere are several di erent types of qubits and this article will be covering the three most common types: electrons in atoms or ions, photons, and superconducting circuits.

The Phase Shift Gate, or the P gate, takes a real number and rotates the qubit around the Z axis of the Bloch Sphere for radians [17]. The Z Gate is equivalent to P(π). To represent 90° degree turns around the Z axis of the Bloch Sphere, the S gate, or the Gate is used which is equivalent to P(π/2) [17]. Similarly, to represent a 45° degree turn, the T gate, or the Gate is used which is equivalent to P(π/4) and the inverse of the T gate, the gate is equivalent to P(-π/4) [17].

Subatomic particles, like electrons, have an inherent property known as spin, which is a type of angular momentum [18]. ey naturally behave as if they are spinning and initially have a non-zero angular momentum despite not rotating around another object [18]. us using the property, we can nd that the electron is either in the spin state ‘spin up’, if it is ‘rotating’ clockwise or the spin state ‘spin down’ if it is ‘rotating’ anticlockwise [18]. e spin states ‘spin up’ and ‘spin down’ corresponds to the | 0 > or | 1 > eigenstates [19]. We can also alter their energy state (switching between their natural state and their “excited” state) using lasers to represent the two eigenstates.

Photons, which are very small ‘packets’ of light, can also be used in several ways to model the two eigenstates [19]. Path qubits model the eigenstates by having a single photon pass through a beam splitter which has two light detectors on their respective sides. is causes either light detector to detect a photon 50% of the time but never at the same time, as the photon cannot be split [20].

Some gates perform operations on two qubits. For example, the controlled-NOT gate or the CNOT gate inverts the other qubit if the indicator qubit is | 1 > [15]. For example, if the indicator qubit is | 1 > and the other qubit is | 0 >, the result would be | 1 1 >.

Another important widely used gate is the SWAP gate which swaps the values of the two qubits with each other [15]. For example, two qubits with states | 1 0 > will result in | 0 1 > after the SWAP gate is applied to it.

e top light detector can represent a | 0 > state and the bottom light detector can represent a | 1 > state [19]. Another property of photons is that they have one of two polarisations (horizontal [H] and vertical [V]) perpendicular to the direction of wave propagation as light is a transverse wave which oscillates. ese photons can also exist in a superposition of the two polarisations or have one of the two polarisations, thus they are known as polarisation qubits. Calculations can be made when passing these photons through a horizontal or vertical polariser. A horizontal polariser will let a photon with a horizontal polarisation through but not a photon with a vertical polarisation and vice versa for the vertical polariser [20]. e probability that a photon with a superposition can pass through the horizontal polariser will be |α|2 whilst the probability it will pass through the vertical polariser will be |β|2 [20].

Unlike classical computers where there are multiple electrons in a DRAM circuit for redundancy in case of electron leaks, qubits in quantum computers can be easily collapsed when they interact with other subatomic particles and struggle to work with bigger bits with more electrons [21]. However, this means that they would be vulnerable to electron leakage. A solution around this is superconducting circuits, which are certain metals that are cooled down to nearly 1°K so that their electrons are joined together as a unit and do not scatter around [21]. We can measure the energy level of the electrons or the direction of current to represent the two eigenstates of the qubit [19, 21].

Figure 4 shows the 3 Pauli Gate Matrixes [15].

Figure 5 shows the Phase Shift Gate Matrix [17].

Figure 6 shows the CNOT Gate Matrix[15]

Figure 7 shows the SWAP Gate Matrix [15].

Figure 8 shows a photon passing through a beam splitter[20]

6. Advantages

One of the most important features of quantum computers is their computational power and speed. Unlike supercomputers, quantum computers can double their computational speed by adding a single qubit [9]. Given that IBM released their 5-qubit quantum computer in May 2016 and has created a computer with 25.4 times more qubits in just over 5 years, the potential for quantum computers is huge [22]. They also have the ability to solve complex problems that have many interacting variables and run multiplex simulations due to superposition and entanglement [23]. For example, Quantum Computing Inc (QCI) has designed quantum computers which have been used to solve a 3854-variable optimization problem with 500 constraints for placing vehicle sensors in a BMW in under six minutes and they were able to find a solution with 96% vehicle coverage with only 15 sensors [24]. Aside from cars, quantum computers can be used in other fields for cryptography, chemistry, medical usage, modelling, forecasting, and much more [6, 23]. Quantum computers also have a lower lower bound than classical computers at regular processes like ordered searching [ log (n) compared to log (n)], comparison-based sorting [O(n) compared to O(n log n)] and element distinctiveness [O(√n) compared to O(n log n)[25] In addition to these advantages, quantum computing is also environmentally friendly and requires only 0.002% of the energy used by a classical computer [26].

7. Disadvantages

Although quantum computers can be used in a variety of different fields, they are unable to solve most problems with 100% accuracy that can be solved with classical computers easily due to their probabilistic nature [16]. Quantum computers are also unable to store data and most memory can only be stored for up to a few hundred microseconds (10-6 s).

To reduce errors in qubits, they also have to be stored in extremely cold temperatures (3 °K) and require huge machinery as well as energy [27]. Although there have been many recent advancements, we are still far away from unleashing the full potential of quantum computing as quantum computers with hundreds or thousands of qubits are extremely complicated and difficult to build as qubits tend to have lower connectivity (communication within qubits) in larger quantum machines [27]. Due to its technical limitations, the difficulty of building a supercomputer and the extreme environment needed to store a quantum computer, a McKinsey report predicts that there will still be less than 5000 quantum computers by 2030, compared to over 2 billion computers today [27]. However, the rise of quantum computing means that many companies will now be at risk of being hacked by quantum computers as they will be able to break current cryptographic algorithms with ease [28]. They are also very expensive and cost tens of millions of dollars for one.

8. Cryptography

Currently, there have been multiple quantum computing algorithms such as Shor’s algorithm and Grover’s algorithm which have been developed to crack encryptions such as RSA (involves multiplying two huge prime numbers together), TDES or AES. Shor’s algorithm helps decrypt encryptions like RSA as it is able to find the decomposition of any integer into two primes in O(d3), where d is the number of digits that the integer has in decimal, which is a massive speedup compared to the exponential time complexity of classical computers [29].This time is very short considering that the upper bound of RSA integers is around 2470 digits long. Grover’s algorithm can help crack symmetric key algorithms with a lower number of bits. Using quantum computation to search for elements in an unstructured database allows for an O(√n) time complexity compared to O(n) in classical computers [30]. Although this is only a quadratic speed-up, this is already enough to crack any key size of TDES and up to 128-bit AES [30, 31]. However, quantum computing is still in its infancy stage and quantum scientists have not been able to use these algorithms to decrypt huge numbers currently used today. Despite this, many companies have invested in quantum-safe algorithms like CRYSTALS-Kyber, CRYSTALS-Dilithium and Falcon [31].

8. Chemistry

In quantum chemistry, ab initio (“from first principles”) calculations try to solve the electronic Schrödinger equation, = , given the position of the nuclei and number of electrons to find its energy and wave function, which can be derived to find electron densities, electron distribution and any other properties of the system [32]. As the calculations are very complex and are probabilistic, quantum computers have been used to represent states of a quantum chemical system to simulate quantum physics. Although current quantum computers have a relatively low number of qubits and have limited gate operations, future quantum computers with more qubits will be able to run a quantum phase estimation (QPE) algorithm which can solve for any variables in polynomial time, a time that is unreachable for classical computers [33]. Currently, quantum computers by IBM have been successful in doing some ab initio molecular dynamic methods (simulation of physical movement of subatomic particles) with fairly high precision on simpler elements like hydrogen and even beryllium hydride [33, 34].

9. Prediction

Weather forecasting, stock market analysis, and predictions are all very complex and take lots of computational power to get an accurate prediction. These can be solved through quantum computing, as properties of superposition allow for the handling of huge numbers of variables interacting in a non-trivial way, which can reduce the damages of natural disasters as the predictions will become more accurate and precise [35]. Through the use of qubits, quantum machine learning algorithms can also be developed for pattern recognition with huge datasets and performing classification of data [35]. This could help increase investment gains, open new investment opportunities and reduce the risk of trading [36]. Additionally, it can help detect fraud (over $10 billion is lost per year due to fraud in the US), money laundering and forecast crashes in the markets which can save billions and billions of dollars [36]. Quantum computers can also help with recommender systems and social media algorithms.

10. Conclusion

Despite the extreme conditions, expenses, and issues raised due to quantum computing such as privacy concerns, quantum computing will surely become one of the most important industries in the world within a decade due to its strong ability to solve very hard optimization problems in a short amount of time. Although quantum computing is still in its infancy, its applications in so many different fields like cryptography, chemistry and forecasting still shock many and are full of potential. Through further research by scientists, I believe that quantum computers with thousands of qubits, which can perform P or even NP problems in very little time, can be made in ten to fifteen years given the exponential growth of quantum computing technology and rising awareness surrounding this technology.

*Note that this article does not cover more advanced topics such as quantum interference or quantum algorithms or applications of quantum gates to make this more simple and digestible for the reader.

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[29] “Shor’s Algorithm - IBM Quantum” IBM Quantum, https://quantum-computing.ibm.com/composer/docs/iqx/guide/shors-algorithm.

[30] Mina-Zicu, M.; Simion, E. Threats to Modern Cryptography: Grover’s Algorithm. Preprints 2020, 2020090677

[31] “What Is Quantum-Safe Cryptography, and Why Do We Need It? | IBM.” IBM - United States, https://www.ibm.com/cloud/blog/what-is-quantum-safe-cryptography-and-why-do-we-need-it.

[32] Cyanide, Mohsin. Ab Initio Calculations and Modelling in Computational Chemistry. YouTube, 9 Jan. 2022, https://www.youtube.com/watch?v=LRK0zgNjPl8.

[33] Fedorov, Dmitry, et al. “Ab Initio Molecular Dynamics on Quantum Computers.” ArXiv.Org, 14 Aug. 2020, https://arxiv.org/abs/2008.06562.

[34]“Science | AAAS.” AAAS, https://www.science.org/content/article/quantum-computer-simulates-largest-molecule-yet-sparking-hope-future-drug-discoveries?cookieSet=1.

[35] Dutta, Aratrika. “Quantum Predictions: Weather Forecasting with Quantum Computers.” Analytics Insight, 27 Sep. 2021, https://www.analyticsinsight.net/ quantum-predictions-weather-forecasting-with-quantum-computers/.

[36] “Quantum Computing Use Cases for Financial Services | IBM.” IBM, https://www.ibm.com/thought-leadership/institute-business-value/report/exploring-quantum-financial.

[37] “The No-Cloning Theorem | Quantiki.” Quantiki | Quantum Information Portal and Wiki, https://www.quantiki.org/wiki/no-cloning-theorem.

the SPEED OF LIGHT and

its significance

by Sky Lee

1. The Universal Threshold

Would you believe me if I told you that the fastest speed in the vast universe is 299 792 458 ms-1, the speed of light, [1] that if something goes faster than that threshold, the universe breaks and reality collapses? The fact that the universe has a speed limit is extremely counterintuitive; it’s hard to picture something travelling at the speed of light and it’s even harder to grasp why nothing can go over that specific limit.

2. Origins

1905 was Einstein’s Annus Mirabilis, his Year of Miracles, [2] in which he published four papers: “On a Heuristic Viewpoint Concerning the Production and Transformation of Light”, “On the Motion of Small Particles Suspended in a Stationary Liquid, as Required by the Molecular Kinetic Theory of Heat”, “On the Electrodynamics of Moving Bodies”, and “Does the Inertia of a Body Depend Upon Its Energy Content?”. These four papers have made a significant impact on the physics community, giving insights in the Quantum Theory of Light and the existence of atoms and molecules. [3] Out of the four papers, “On the Electrodynamics of Moving Bodies” is probably the one that stands out most. Why, you may ask, because it includes the most famous equation in the world, E=mc2, the embodiment of the renowned Special Relativity and is the key to understanding how this universe operates.

3. The Speed of Light as an Invariant

Einstein’s Special Relativity shows the connection between some of the most significant quantities in the universe, mass, time, and space without the complication of gravity (relativity considering gravity is known as General Relativity). [4] Special relativity is based on the fact that the speed of light is a constant for all observers when gravity is not taken into consideration (curved light gets slowed down when it is not observed from one specific local reference frame according to the Shapiro Time Delay, assuming the presence of gravity) (fig A). [5] The constant c was calculated by Scottish physicist James Clerk Maxwell with the following equation (fig B).

4. Spaceship and Planet Analogy [6]

Consider a spaceship moving relative to a hypothetically stationary planet (fig. C), according to Einstein’s First Postulate of Special Relativity, the laws of physics are the same and can be stated in their simplest form in all inertial frames of reference [7].Thus, in this situation there is no way we can determine whether the planet is stationary, and the plane is moving or vice versa. Now imagine a ball being thrown across in the spaceship, the relative speed of the ball as observed from the planet, according to the Galilean Transformation, is the speed of impulsion of the ball combined with the speed of the spaceship itself. On the other hand, the relative speed of the ball as observed locally in the spaceship is just the speed of impulsion of the ball. With that said, the relative speed of the ball is lower if observed locally in the spaceship.

Instead of a ball being thrown in the spaceship, imagine a beam of light being shone across in the spaceship (fig. D). Intuitively, we would consider the beam of light as a travelling particle, just like the ball, and thus, assume that the relative speed of the beam of light is lower if observed locally in the spaceship. Yet, that contradicts Maxwell’s calculations of a constant speed of light c, for every observer, when gravity is not taken into consideration. So, is the speed of light c, still a constant? If it is, then classical Newtonian mechanics would simply be paradoxical. This is where special relativity comes in, a scientific principle which accommodates Maxwell’s constant speed of light and the validity of classical mechanics.

With the fact that the speed of light is constant in mind, we can move on to understanding Special Relativity with the ‘spaceship and planet’ analogy.

fig. A Shapiro time delay [5]

fig. B

fig. D A beam of light being shone across the spaceship [6]

fig. C A moving spaceship relative to a planet [6]

There are so many reasons why nothing can go faster than the speed of light. With that said, there is only one particular physical phenomenon that explains why only massless objects like photons can travel at the speed of light, that is Relativistic Kinetic Energy.

Rest mass energy is the energy (fig. E) that all matter possesses (i.e., as long as it has mass and takes up space), be it matter that is stationary or matter that has motion. Relativistic energy (fig. F) is the energy that every moving object possesses. Relativistic kinetic energy (fig. G) is the energy every object possesses strictly due to their motion (i.e., the object’s rest mass energy is excluded). What is the significance of that, you may ask. As seen in the relativistic kinetic energy equation, as the speed of the object v increases, v2 also increases, as v approaches c, the Lorentz Factor, γ tends to infinity. This implies that if an object has to travel at the speed of light, the required energy tends to infinity (fig. I). As it is impossible to supply an infinite amount of energy to anything, it is simply unfeasible for matter to travel at the speed of light.

6. Side Effect of Travelling at c: Time Dilation

Imagine a person travelling near the speed of light, Alice, and a stationary person. They experience time differently according to time dilation in Einstein’s Special Relativity.

If Alice is travelling in a spaceship at the speed of 0.9c, 90% the speed of light, then it would take her 1 second to travel a distance of 0.9c metres (ignoring the effects of relativistic kinetic energy). In this case, T, the time in Alice’s frame of reference is 1 second. Yet to stationary observer Bob, it takes Alice 2.29 seconds to travel a distance of 0.9c metres according to the Time Dilation Equation (fig. J).

What is more fascinating is that Alice or Bob could technically be the stationary observer in this case according to Einstein’s First Postulate of Special Relativity. In Alice’s frame of reference, she is stationary and Bob is moving at 0.9c, while in Bob’s frame of reference, he is stationary and Alice is moving at 0.9c. This implies that to Bob, time flows slower in his frame than in Alice’s frame. While to Alice, time flows slower in her frame than in Bob’s frame.

7. Breaking Causality and the Emergence of Time Paradoxes, a Result of Time Dilation

Cause has to come before effect in Physics. Person A would never receive a message before Person B sends it to him, your table never gets wet before you spill the water, and a person’s head wouldn’t explode before a bullet hits him. Causality governs how the Universe operates, it is that one rule which cannot be broken. Imagine your friend, Jonathan, receiving your text message before you’ve even pressed the ‘send’ button, that’s crazy!

If an object travels faster than the speed of light, causality would be broken, or in other words, the Universe goes nuts. There is not much mathematical proof on how going faster than the speed of light breaks causality, a simple analogy and example can perfectly illustrate the correlation.

Before we move on to the example, we first have to understand Spacetime Diagrams. For every object, the horizontal line represents the change in space in its frame of reference while the vertical line represents the change of time in its frame of reference. For a stationary object, a vertical line represents its activity in spacetime. fig. K Spacetime Diagram [10]

fig. I graph of Kinetic energy against Speed [9]

Continuing with the example of Alice and Bob [11]. Imagine in a new scenario, Alice standing stationary on planet Earth and Bob moving at 0.87c away from Earth relative to her. In Alice’s frame of reference, she can be represented by a vertical line while Bob can be represented by a line of slope magnitude greater than 1. In Bob’s frame of reference, he can be represented by a vertical line while Alice can be represented by a line of slope magnitude greater than 1. Again, Einstein’s First Postulate of Special Relativity tells us that Alice can be stationary in her own frame of reference (fig. L) while Bob can also be stationary in his (fig. M). According to the Time Dilation Equation, in Alice’s frame of reference, 2 seconds for her is 1 second for Bob while in Bob’s frame of reference, 2 seconds for him is 1 second for Alice.

Enter FTL, Faster Than Light. Imagine there was something much faster than light, something that is instantaneous. An object travelling instantaneously can be represented as a horizontal line in spacetime diagram as an object travels an infinite distance in space without travelling in time. Imagine Alice sending an instantaneous message to Bob. If she sends the message to Bob, at 4 seconds on her clock (i.e. in her frame of reference), then Bob would receive her message at 2 seconds on his clock, if we consider this situation in Alice’s frame of reference (fig. N). Things start to get weird when we look at the message from Bob’s frame of reference, we can see that the message is sent from 4 seconds on Alice’s clock to 2 seconds on Bob’s clock, in other words, the message is sent from 8 second on Bob’s clock to 2 seconds on the same clock, the message has travelled back in time (represented by a negative slope) (fig. O) in Bob’s frame of reference! Now imagine Bob taking two seconds to read the message Alice sent him, and at 4 seconds on his clock, decides to send an instantaneous reply back to Alice. She would receive it at 2 seconds on her clock, meaning that she received a reply from Bob even before she sent the message (i.e. at 4 seconds on her clock in her frame of reference). Causality has been broken (fig. P) because of special relativity and the type of messaging system that can travel faster than the speed of light, in this example, at instantaneous speed.

fig. L Alice’s frame of reference [11]

fig. N Alice’s frame of reference [11]

fig. M Bob’s frame of reference [11]

fig. O Alice’s message travelling back in time in Bob’s frame or reference [11]

fig. P Causality has been broken

8. Insights

The speed of light is so much more than just a number used in calculations in physics tests, it is a value that governs how the universe operates and ensures effect comes after cause. It explains why you will never get a reply before you send a message, as there is nothing that can travel faster than the speed of light in this universe. While popular movies these days have explored the ideas of time travelling and travelling at the speed of light, the current physical laws remain unchanged, telling us concrete and undeniable facts about the universe: travelling quicker than the speed of light just isn’t feasible. ‘First comes the Physics, then comes the Engineering’, should humans endeavour on travelling at the speed of light, the fundamental laws of physics established by the great scientist, Einstein will have to be broken and overthrown.

9. Bibliography

[1] Wikipedia, “Speed of light”, accessed 2022 November 9, https://en.wikipedia.org/wiki/Speed_of_light

[2] npr, Richard Harris, “Albert Einstein’s Year of Miracles: Light Theory”, 2005, March 17, accessed 2022 November 9, https://www.npr. org/2005/03/17/4538324/albert-einsteins-year-of-miracles-light-theory#:~:text=Scientists%20call%201905%20Albert%20Einstein’s,the%20 famous%20equation%20E%3Dmc%C2%B2.

[3] Wikipedia, “Annus Mirabilis papers”, accessed 2022 November 9, https://en.wikipedia.org/wiki/Annus_mirabilis_papers#:~:text=The%20 annus%20mirabilis%20papers%20(from,the%20foundation%20of%20modern%20physics.

[4] Space, Vicky Stein, “Einstein’s Theory of Special Relativity”, 2021 September 21, accessed 2022 November 9, https://www.space. com/36273-theory-special-relativity.html#:~:text=Special%20relativity%20is%20an%20explanation,equation%20E%20%3D%20mc%5E2.

[5] Universerio@YouTube, “What is the true meaning of constant speed of light? Why is the Speed of Light Constant?”, 2022 August 22, accessed 2022 November 9, https://youtu.be/hvMAT1xeraM

[6] ScienceClic English@YouTube, “Special Relativity”, 2019 September 10, accessed 2022 November 9, https://www.youtube.com/watch?v=uTyAI1LbdgA

[7] Douglas College Physics 1207, 13.1 Einstein’s Postulates, no date, accessed 2022 November 9, https://pressbooks.bccampus.ca/introductorygeneralphysics2phys1207opticsfirst/chapter/28-1-einsteins-postulates/#:~:text=The%20first%20postulate%20of%20special,relative%20motion%20 of%20the%20source.

[8] For the Love of Physics@YouTube, “Relativistic Kinetic Energy | Answer to why nothing can travel faster than the speed of light?”, 2021 July 3, accessed 2022 November 9, https://www.youtube.com/watch?v=TwKSGVKfIXw

[9] LibreTexts Physics, “Relativistic Quantities”, 2020 November 6, accessed 2022 November 10, https://phys.libretexts.org/Bookshelves/University_Physics/Book%3A_Physics_(Boundless)/27%3A__Special_Relativity/27.3%3A_Relativistic_Quantities

[10] Wikipedia, “Spacetime Diagram”, accessed 2022 November 20, https://en.wikipedia.org/wiki/Spacetime_diagram

[11] Arvin Ash@YouTube, “How Faster than Light Speed Breaks CAUSALITY and creates Paradoxes”, 2021 June 25, accessed 2022 November 20, https://www.youtube.com/watch?v=mTf4eqdQXpA&t=744s

CHEMISTRY BIOLOGY and

Introduction

How would you feel if you had the skin of a 20-year-old when in reality you are 50? Many would love to attain this level of collagen in their skin. Not long ago, scientists in Cambridge successfully 1rejuvenated a 53-year-old woman’s skin cells to the equivalent of a 23-year-old’s using cell reprogramming.

This newfound success could not only contribute to the cosmetic field, but also help future generations look younger.

This article will explain to you the start of cellular reprogramming, the current findings and the future of how this one of a kind technology could benefit everyone’s health and happiness.

The Origin of Cellular Reprogramming

Cellular reprogramming is the process of converting a mature, specialised cell into an embryonic-like stem cell. The concept of rejuvenation and cellular reprogramming was first proposed by John Gurdon in the 1960s. He removed the nucleus of a fertilised egg cell from a frog and replaced it with the nucleus of a cell taken from a tadpole’s intestine, where the modified egg cell grew into a new frog.

In 1997, a team of scientists and researchers led by Professor Sir Ian Wilmut at the Roslin Institute in Edinburgh cloned an adult sheep called Dolly. This research breakthrough grabbed headlines around the world. Wilmut’s team tried to develop a better method to produce genetically modified livestock. 2 By turning an adult mammary gland cell taken from a sheep into an embryo, Dolly was created. 3

She was the first mammal to be cloned from an adult cell. Dolly’s birth proved that specialised cells could be used to create an exact copy of the animal they came from. With this knowledge, it proved that turning a differentiated cell back into any kind of cell could open up many opportunities, especially in biology and medicine, for example, treating diseases like spinal cord injury.

Gene regulatory networks and tissue morphogenetic events drive the emergence of shape and function, allowing scientists to mimic and manipulate human embryos. This also means that we could potentially turn an old cell into a younger cell.

In 2006, a new method, Induced Pluripotent Stem cells (iPS), was discovered by Shinya Yamanaka. iPS cells have the potential to develop into every type of cell in the body and are valuable tools for disease modelling, drug screening, and cell therapy. 4iPS cells also provide further opportunities for discovery in life science such as creating great potential in regenerative medicine.

LOOK YOUNG?

by Bernice Ho

Figure 1 shows how iPS cells could differentiate into specialised cells like neural cells, Adipocytes and Cardiomyocytes etc.

Figure 2: Stem cell biology

e aim of cell reprogramming is to convert 5stem cells to desired cell types. e most direct way of di erentiating 6stem cells is to mimic the development of an inner cell mass during gastrulation. During gastrulation, pluripotent stem cells di erentiate into ectodermal, mesodermal, or endodermal progenitors. Mall molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. But, of course, there are many other ways of di erentiating a stem cell.

Turning Back the Ageing Clock

On 8th April 2022, scientists from the Babraham Institute, and a life sciences research institute in Cambridge, published an article on eLifesciences. The research team successfully 7rejuvenated a 50-year-old woman’s skin cells into behaving and looking as if they came from a 23-year-old in only 13 days.

Not only have they furthered the use of IPS cells, they have even developed the 8first ‘maturation phase transient reprogramming’ (MPTR) method, where reprogramming factors were expressed until a certain rejuvenation point followed by withdrawal of their induction. Cells’ fibroblast identity was found to be temporarily lost and then re-acquired during MPTR. This could be a result of epigenetic memory at enhancers and/or persistent expression of some fibroblast genes through using dermal fibroblasts from middle age donors. Amazingly,9 their method substantially rejuvenated multiple cellular attributes including the transcriptome (the array of mRNA transcripts produced), which was rejuvenated by around 30 years as measured by a novel transcriptome clock (Aging clock dissociates biological from chronological age).

However, for now, 10the MPTR technique will not be ready for use in clinics due to the potential increases in the risk of cancer brought on by genetic changes within the cells. Yet, scientists are confident that they can find a safer method to rejuvenate cells, and believe that they can apply the same technique to other tissues in the body. Ultimately, scientists are hoping to develop treatments for age-related diseases such as diabetes, heart diseases, and neurological disorders.

https://www.sciencealert.com/scientists-rewind-the-age-of-human-skin-cells-back-30-years

Potential applications of cell reprogramming

Cell reprogramming has the potential to become huge in the medical eld as iPS cells play a vast role in developing restorative medicine. 11Serious medical conditions, like cancer, are caused by improper di erentiation or cell division. Even though cell reprogramming isn’t vastly used to cure cancer, currently, several stem cell therapies are possible, among which are treatments for spinal cord injuries and heart failure12.

By furthering study in cell reprogramming, we may be able to nd a cure for chronic diseases. One example is Alzheimer’s disease (AD), which is the most prevalent age-related dementia in the world. e underlying mechanisms of AD remain unclear. In recent years, upon the improvement of induced pluripotent stem cell technology and direct cell reprogramming technology, it has become possible to induce non-neuronal cells, such as broblasts or glial cells, directly into neuronal cells in vitro and in vivo. e induced neuronal cells are functional and can integrate into the local neural net. ese incredible ndings are encouraging and can provide a new clinical approach to treating AD.

https://www.kindpng.com/imgv/hbwmixJ_picture-cancer-vs-normal-cell-division-hd-png/

Other than being able to use cell reprogramming in the medical eld, 13cell reprogramming also gives a plausible answer for avoiding the use of human embryonic cells in experimental research and clinical medicine, which is ethically unacceptable, as obtaining these cells requires the destruction of human embryos. Cell reprogramming is considered a much better option than the use of embryonic stem cells.

Figure 2: Collagen production (in red) being restored in cells after reprogramming. (Fátima Santos, Babraham Institute)

Figure 3: Normal cell division vs cancer cell division

Conclusion

Cell reprogramming has led to many new findings, for example, cell rejuvenation of a 50-year’s old woman’s skin cells into a 23 year old’s skin in a very short period of time. Even though cell rejuvenation is just a very small part of cell reprogramming, there are many things to explore within this research field. Hopefully, in the near future, cell reprogramming will be able to be used in many different therapeutic areas to improve our healthy lifespan and save thousands of lives.

Bibliography

[1]“Rejuvenation of Woman’s Skin Could Tackle Diseases of Ageing.” BBC News, 8 Apr. 2022, www.bbc.com/news/science-environment-60991675.

[2]“Rejuvenation of Woman’s Skin Could Tackle Diseases of Ageing.” BBC News, 8 Apr. 2022, www.bbc.com/news/science-environment-60991675.

[3]Roslin Institute. “The Life of Dolly | Dolly the Sheep.” Ed.ac.uk, 2019, dolly.roslin.ed.ac.uk/facts/the-life-of-dolly/index.html.

[4]“Shinya.yamanaka@Gladstone.ucsf.edu.” Gladstone.org, gladstone.org/people/shinya-yamanaka#:~:text=In%202006%2C%20Shinya%20 Yamanaka%20discovered.

[5]Zakrzewski, Wojciech, et al. “Stem Cells: Past, Present, and Future.” Stem Cell Research & Therapy, vol. 10, no. 1, 26 Feb. 2019, stemcellres. biomedcentral.com/articles/10.1186/s13287-019-1165-5, 10.1186/s13287-019-1165-5.

[6]Zakrzewski, Wojciech, et al. “Stem Cells: Past, Present, and Future.” Stem Cell Research & Therapy, vol. 10, no. 1, 26 Feb. 2019, stemcellres. biomedcentral.com/articles/10.1186/s13287-019-1165-5, 10.1186/s13287-019-1165-5.

[7]“Rejuvenation of Woman’s Skin Could Tackle Diseases of Ageing.” BBC News, 8 Apr. 2022, www.bbc.com/news/science-environment-60991675.

[8]Gill, Diljeet, et al. “Multi-Omic Rejuvenation of Human Cells by Maturation Phase Transient Reprogramming.” ELife, vol. 11, 8 Apr. 2022, 10.7554/elife.71624. Accessed 13 Apr. 2022.

[9]Gill, Diljeet, et al. “Multi-Omic Rejuvenation of Human Cells by Maturation Phase Transient Reprogramming.” ELife, vol. 11, 8 Apr. 2022, 10.7554/elife.71624. Accessed 13 Apr. 2022.

[10]“Rejuvenation of Woman’s Skin Could Tackle Diseases of Ageing.” BBC News, 8 Apr. 2022, www.bbc.com/news/science-environment-60991675.

[11]Zakrzewski, Wojciech, et al. “Stem Cells: Past, Present, and Future.” Stem Cell Research & Therapy, vol. 10, no. 1, 26 Feb. 2019, stemcellres. biomedcentral.com/articles/10.1186/s13287-019-1165-5, 10.1186/s13287-019-1165-5.

[12]Menasché, Philippe, et al. “Human Embryonic Stem Cell-Derived Cardiac Progenitors for Severe Heart Failure Treatment: First Clinical Case Report: Figure 1.” European Heart Journal, vol. 36, no. 30, 19 May 2015, pp. 2011–2017, academic.oup.com/eurheartj/article/36/30/2011/2398140, 10.1093/eurheartj/ehv189.

[13]Aznar Lucea, Justo, and Miriam Martínez. “[Ethical Reflections on Cell Reprogramming].” Cuadernos de Bioetica: Revista Oficial de La Asociacion Espanola de Bioetica Y Etica Medica, vol. 23, no. 78, 2012, pp. 287–299, pubmed.ncbi.nlm.nih.gov/23130744/. Accessed 29 Nov. 2022.

New Treatments for CANCER ?

by Audrey Lai

Introduction

Nearly 10 million people die from cancer every year, making it the second most common cause of death in the world.1 Chemotherapy, radiation therapy, and surgery have been the traditional treatments for cancer since the 20th century and are still commonly used today. However, as many already know, the effectiveness of these traditional cancer treatments is often limited. Thanks to the quick development of technologies and medical discoveries, there are currently new, promising methods for treating cancer which includes immunotherapy, a modern medical innovation. In this article, we will explore what cancer is, how traditional cancer treatments work, and why we need immunotherapy, such as monoclonal antibodies and CAR T-cell therapy. First of all, what is cancer?

Cancer

Cancer is a non-communicable disease in which body cells grow and divide uncontrollably, spreading to other parts of the body via the bloodstream. Human body cells undergo mitosis, also known as cell division, in order to grow and repair old, damaged cells. A mutation in the gene that regulates a cell’s functions and division results in cancer. Genes involved in regular cell growth can become oncogenes or healthy tumour suppressor genes can become inactive as a result of a change in the DNA. Consequently, this mutation will cause uncontrolled cell growth. Gene mutations can result from random errors during cell division, damage to DNA caused by carcinogens such as tobacco, or inheritance from one’s parents. Cancer cells that have detached from their primary tumour and travelled through the bloodstream to form secondary tumours in other parts of the body are said to have metastasized.

Traditional Treatments

Surgery, chemotherapy, and radiation have always been popular options in treating cancer, yet the chances of a patient with cancer dying of it are similar to those of 50 years ago.2 First, chemotherapy works by using chemicals to shrink tumours, destroy or kill cancer cells, and help other treatments work better. However, the main drawback of chemotherapy is that it simultaneously kills cancer and healthy cells that grow and divide quickly, such as hair, skin, blood and intestinal cells. As a result, it leads to potential side effects like hair loss, nausea, fatigue, and infections. Second, radiation therapy works by using radiation to shrink tumours and slow the growth of cancer cells by damaging their DNA. It is a local treatment and can be given externally or internally. The disadvantages include damaging surrounding healthy cells, leading to side effects and patients also have a lifetime dose limit to the amount of radiation that can be received by the body. Third, surgery is another option for removing tumours grown from cancer cells. A limitation of surgery is that blood cancer or metastatic cancer that has spread cannot be treated with surgery. This makes surgery only available for removing solid, local tumours in the body. Therefore, targeted therapy like immunotherapy is designed to treat targeted cancer cells.

Immunotherapy

The immune system helps detect and destroy any foreign or abnormal cells in our body including cancer cells. Immunotherapy is a type of cancer treatment, which aims to encourage the patient’s immune system to target cancer cells and destroy them. The treatments are designed to target a specific antigen on a specific type of cancer cell while sparing healthy body cells. Immunotherapy includes cancer vaccines, adoptive cell therapy (CAR T-cell therapy), checkpoint inhibitors and monoclonal antibodies. Over 100 different types of cancer exist today, which is a significant number. 3Therefore, since each type of cancer can be significantly distinct, a more targeted and focused approach is needed.

Monoclonal Antibodies

One of the popular methods of immunotherapy is monoclonal antibodies. Did you know that the EU and the US have approved around 100 therapeutics monoclonal antibodies for treating both cancer and non-cancer diseases? 4Monoclonal antibodies are becoming more and more common in the field of medicine due to their ability to bind to a specific protein or antigen on cell membranes. Other applications of monoclonal antibodies include the delivery of medications to cancer cells, the attachment of fluorescent substances to detect specific cells, pregnancy testings, and the diagnosis of numerous diseases such as HIV.

How are monoclonal antibodies produced?5

1. A type of antigen on the cancer cell is injected into mice and their B-cell lymphocytes are stimulated to produce the antibodies for the specific antigen.

2. The mice undergo blood screening for the antibody production.

3. The splenocytes which produce the B-lymphocytes are removed.

4. The splenocytes are fused with myeloma cells, which can divide unlimitedly, forming hybridoma cells.

5. The hybridoma cells divide and produce many clones specific to cancer’s antigen.

6. The clones are screened and selected, then purified. As a result many clones of antibodies are made.

How do monoclonal antibodies work in the body?

1. Monoclonal antibodies are injected into the patient’s bloodstream.

2. They will locate proteins called antigens on cancer cells.

3. Since the monoclonal antibodies are specific to the antigen on cancer cells they will bind and form an antibody-antigen complex.

4. The antibody will then signal other immune cells.

5. The immune cells will arrive and help destroy cancer cells.

Monoclonal antibodies treatment in cancer:

In recent years, monoclonal antibodies have become an option for treating cancers. An example is rituximab (Rituxan), a monoclonal antibody targeting leukaemia and B-Cell non-Hodgkin lymphoma (NHL). According to a study, patients with lymphomas who received rituximab and chemotherapy had a better survival rate than those receiving chemotherapy.6

Car T-Cell Therapy

Did you know since 2017, six CAR T-cell therapies have been approved by the FDA for the treatment of blood cancers? 7Acute lymphocytic leukaemia has a 40% 5-year survival rate for people aged 20 and older.8 However, blood cancer is now incredibly manageable due to decades of research and the introduction of innovative treatments like CAR T-Cell therapy.

How are CAR T-cells made:

1. Blood is drawn from a patient which moves through a blood separator to collect the T-cells, the remaining blood components will return to the blood.

2. The T-cells are genetically engineered by editing their gene to produce a protein on their surface (chimeric antigen receptors) which bind to specific proteins or antigens on the cancer cells.

3. Genetically modified T-cells are grown until there are millions of them and then they are collected.

How CAR T-cells work in the body:

1. After producing the CAR T-cells, they are reinfused back into the patient’s blood.

2. In the body, the CAR T-cells will bind to proteins on the cancer cells.

3. This will signal the immune system to destroy them.

CAR T-cell therapy treatment in cancer:

tisagenlecleucel is a CAR T-cell medication to treat B-cell acute lymphoblastic leukaemia. In 2021, a patient in Hong Kong was successfully treated with tisagenlecleucel (Kymriah). 9After relapsing twice from chemotherapy and haematopoietic stem cell transplantation, he was recommended CAR-T cell therapy. After the treatment, he recovered without experiencing any serious complications and results from bone marrow examinations show that no leukaemia cells could be found.

Modern VS Traditional

On one hand, immunotherapy seems to be a modern, better treatment due to its capability to target particular cancer cells while sparing healthy cells. This makes patients receiving targeted therapy experience fewer and less severe side effects compared to chemotherapy. However, there are a lot of drawbacks to the treatment. Decades of study, several pharmacological trials, and substantial financial resources are needed to develop a drug. Hence, immunotherapy is quite costly and out of reach for many individuals. For example, targeted therapy drugs like trastuzumab (Herceptin) for breast cancer costs $500,000 HKD per year and sorafenib (Nexavar) for liver cancer costs $150,000 HKD per month.10 This raises ethical issues because it is unfair that only wealthy people are able to access the latest advanced treatments for cancer. Conversely, there are also some highly effective traditional treatments even when they cannot specifically target cancer cells. In order to reduce costs and give all citizens an equal chance to obtain cancer treatment, a possibility is for the government to invest more in subsidising cancer treatment research. To conclude, both traditional and immunotherapy treatments for cancer could be used.

Bibliography

[1] WHO International Agency for Research on Cancer. “WHO International Agency for Research on Cancer.” “Cancer Today.” Published 2020. Global Cancer Observatory, https://gco.iarc.fr/today/online-analysis-pie?v=2020&mode=population&mode_population=income&population=900&populations=900&key=total&sex=0&cancer=39&type=1&statistic=5&prevalence=0&population_group=0&ages_ group%5B%5D=17&nb_items=7&group_cancer=1&include_nmsc=1&include_nmsc_other=1&half_pie=0&donut=0.

[2] Goodman, Amy, et al. “Why the ‘Slash-Poison-Burn’ Approach to Cancer Has Failed.” Truthout, Truthout, 23 Dec. 2019, https://truthout. org/video/why-the-slash-poison-burn-approach-to-cancer-has-failed/.

[3] “What Is Cancer?” National Cancer Institute, https://www.cancer.gov/about-cancer/understanding/what-is-cancer#:~:text=There%20 are%20more%20than%20100,cancer%20starts%20in%20the%20brain.

[4] “UpToDate.” Www.uptodate.com, www.uptodate.com/contents/overview-of-therapeutic-monoclonal-antibodies/print#:~:text=Since%20 1985%2C%20approximately%20100%20monoclonal.

[5] “Monoclonal Antibody Production.” Molecular Devices, https://www.moleculardevices.com/applications/monoclonal-antibody-production#gref.

[6] Schulz, Holger, et al. “Chemotherapy plus Rituximab versus Chemotherapy Alone for B-Cell Non-Hodgkin’s Lymphoma.” Cochrane Database of Systematic Reviews, vol. 2010, no. 1, 17 Oct. 2007, www.ncbi.nlm.nih.gov/pmc/articles/PMC9017066/, 10.1002/14651858.cd003805.pub2.

[7] “Car T Cells: Engineering Immune Cells to Treat Cancer.” National Cancer Institute, https://www.cancer.gov/about-cancer/treatment/research/car-t-cells#:~:text=Since%202017%2C%20six%20CAR%20T,%2C%20most%20recently%2C%20multiple%20myeloma.

[8] “Leukemia - Acute Lymphocytic - ALL - Statistics.” Cancer.net, 25 June 2012, www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all/ statistics#:~:text=The%205%2Dyear%20survival%20rate%20for%20people%20age%2020%20and.

[9] “HKUMED Introduces Hong Kong’s First Car-T Cell Therapy for Blood Cancer Patients.” HKU Li Ka Shing Faculty of Medicine, 10 Feb. 2021, https://www.med.hku.hk/en/news/press/20210210-hk-first-car-t-cell-therapy-for-blood-cancer-patients.

[10] “Targeted Therapy Drug: Cancer Treatment, Cost & Funding in Hong Kong.” Www.cigna.com.hk, www.cigna.com.hk/en/smarthealth/medical/targeted-therapy-drug-cancer-treatment-cost-funding-in-hong-kong.

Life Through the ART BUILDING DESIGN

Sustainable

by Kate Xiao

A brief summary of the principles behind carbon neutral buildings and how they will help us establish a cleaner way of living.

Assessing the environmental impact of buildings

In the contemporary world, buildings are responsible for more than 40% of energy usage and 33% of total greenhouse gas emissions in both developed and developing countries.1 According to the U.K Green Building Council, the construction sector uses more than 400 million tons of materials a year, many of which, such as aluminium, concrete, and steel, have an adverse impact on the environment through their high concentration of embodied carbon content (which refers to the greenhouse gas emissions arising from the manufacturing, transportation, installation, maintenance and disposal of a specific building material), with 9.8 million tons of CO2 produced by 76 million tons of finished concrete in the US.2

Fortunately, this data has not gone unnoticed. In the UK, after the launch of the Green Guide to Specification, Oxford Brookes University and the UK construction industry set out regulations to use certain materials in order to reduce the environmental impact, 230,000 construction projects have improved their environmental standing.2 In the US, the Environmental Protection Agency(EPA) also published a number of rules to reduce negative environmental effects (which includes areas such as soil stabilization, erosion and sediment controls, water contamination and waste management). The EPA also has a Greenhouse Gas Reporting Program (GHGRP), where relevant information is gathered every year from large GHG emission sources and reported to the public every October. This can help organisations and companies keep track of GHG emission states and alter the way of maintenance accordingly.

Before the construction of a building, a life cycle assessment (LCA) is carried out to determine the environmental impact it will bring during its lifetime, from designing to demolishment. A LCA is able to assess energy consumption and environmental impact through a scope of analysis with each type of building and fabrication method and each type of manufacturing or building material. With acknowledgement to different effects building materials and dimension choices will bring, designers can alter their scheme at an early stage and plan to embody the most impact reductions as possible.

What is a carbon neutral building?

The definition of a carbon neutral building is a building specifically designed to minimise greenhouse gases at all stages. As opposed to the commuter towns left from the Industrial Revolution and rapid urban development in the 21st century, a new trend in urban planning is led by urban projects that aim to reduce the negative impacts on the environment: The construction of sustainable buildings, carbon neutral buildings, eco-neighbourhoods, and more is highly commended on an international basis.

The principles behind carbon neutral buildings

If other buildings aim to reduce its environmental impact to the minimum, carbon neutral buildings aim to achieve net zero carbon emission. All the climate budget from materials manufacturing, transportation, construction process, and building in operation will be counteracted by investing in renewable energy, using timber as carbon storage, engaging in innovative and novel environmentally-friendly technology (examples are listed in case study below). The point is that over the years, net carbon emission remains zero, achieving carbon neutrality.

Case study: Hong Kong

In Hong Kong, the first carbon neutral building—CIC-Zero Carbon Park—was built in 2012.3

Aside from serving as an exhibition, education and information center, CIC-ZCP acts as a test bed for state-of-the-art eco-building design. A native urban woodland in the middle of the compact, densely populated city, 47% of CIC-ZCP land area is covered in greenery, attracting birds and other animals to create a more biodiverse environment.3 The whole building relies on on-site renewable energy generated from photovoltaic panels and a tri-generation system using biofuel.

Active Systems

Modular Integrated Construction – MiC is an innovative construction method whereby free-standing integrated modules are manufactured in a prefabrication factory and then transported on site for installation in a building.4

The emMiC system in CIC-ZCP makes use of a stormwater box culvert as the heat extraction and rejection media of the Air-conditioning system.5

In an air-conditioner, hot air in the room is sucked in by a grill located on the bottom of the indoor unit, which then flows through some pipes through which the refrigerants also flow in (the most common refrigerant gases include HFCs R-410A, CFCs such as R-22 and hydrocarbons such as R-290). The refrigerant fluids absorb the heat from the hot air and become hot gases themselves. After passing through the compressor, the hot gas reaches the condenser in the air-conditioner and condenses to cooled liquid. The stormwater, which is relatively low in temperature (about 20 degrees Celsius), serves as an excellent condensing medium for the air conditioner.

Fig. 1 CIC-ZCP energy system

Compared with a typical AC system/electrical heating system, emMiC can reduce energy consumption by 50% and 70% for cooling and heating respectively5 . Using stormwater as a condensing medium also saves fresh water sources, avoids Legionnaire’s disease and mitigates the urban heat island effect*.

*(Urban) Heat island effect: the effect that cause an area of higher temperature relative to surrounding areas, occurs when high concentration of buildings, pavements and other man-made infrastructures absorb and maintain heat radiation.

Air Improvement Photovoltaic (AIPV) Glass Canopy

CIC-ZCP adopts the Cadmium Telluride nano thin-film photovoltaic technology to generate renewable energy from solar power.

Cadmium Telluride (CdTe) solar cells contain thin-film layers of CdTe material as a semiconductor to convert absorbed solar energy into electricity. This type of solar cell is separated into 5 layers: a copper-doped carbon paste cathode (back content), p-type cadmium telluride and n-type cadmium sulfide (CdS) layers in the middle, a tin oxide or cadmium-based stannous oxide transparent layer acting as the anode (front content), and finally glass substrate on the outside.7

8Among all polycrystalline compound semiconductors, CdTe has become a proven TFSC material for its potentiality in several of its advantages and easier methods of thin film depositions:

- An ideal solar cell has a direct band gap of 1.4 eV to absorb the maximum number of photons from the sun’s radiation. CdTe has a near optimum band gap of 1.44 eV, which, compared to the most widely used material – silicon – in the PV industry (indirect band gap of 1.1 eV), is a much more suitable fit in electricity production.8

- CdTe has a high absorption coefficient due to its short absorption length. It absorbs over 90% of accessible photons (hv > 1.44 eV) in a 1 μm thickness.

- The economic cost of producing CdTe cells (associated with polycrystalline and glass) is much lower than the production involving bulk silicon.

- The polycrystalline layers of a CdTe solar cell can be deposited via many different techniques (such as closed-spaced sublimation, physical vapor deposition, RF magnetron sputtering and more).

Passive Designs

Cross Ventilated Layout

Cross ventilation is a natural method of cooling the inside of a building —a method that doesn’t require any maintenance cost, carbon emission, or energy consumption, yet still is effective.

The system relies on wind to force external cool air into the building through an inlet (such as a window or wall louver). When this happens, the two sides of the building will be hit with different amounts of pressure. The pressure change will hence force air to the area with lower pressure, which is where the outlet (such as a higher window opening) is located.9 The air circulation allows the inside of the building to experience cool breezes (This is why you will experience breezes when having both the window and room door open).

CIC-ZCP locates its main façade to face the southeast to increase efficiency, as the prevailing summer breeze comes from that direction. Compared to a conventional building, the building’s cross ventilated layout is estimated to have reduced the need for air-conditioning by over 34%.3

Fig.2 emMiC operation system

Fig.3 Schematic view of CdS/CdTe thin-film solar cell

Fig. 4 Band energy diagram of the CdS/CdTe solar cell

Wind Catcher

A wind catcher is a small chimney fitted on the roof of the building. As the velocity of wind flowing over the roof is greater than the lower windows of the building, air in the shaft is forced down to cool the building. External air from the roof improves the ventilation potential for areas furthest away from the windows and therefore is not touched on by the cross-ventilation system.

Renewable Energy

Renewable energy is a natural energy that will never deplete and can be used again and again. Many practices were taken to increase the use of renewable energy on site, including but not limited to:

- ZCP has its energy generated mainly from biodiesel. Biodiesel is a type of diesel fuel derived directly from plants and animals, or indirectly from agricultural, industrial, domestic, or commercial waste, and consisting of long chain fatty acid esters. The biodiesel tri-generation system on site is estimated to supply over 129% of ZCP’s energy demand.3

· Different areas of the building are assessed to investigate the irradiance level, and 3 types of pho tovoltaic panels are used based on study. Polycrystalline Silicone PV panels, Building Integrated Photovoltaics, and cylindrical CIGS thin film PV panels are integrated to the inclined main roof, viewing deck, and Air-Tree installation respectively. The PV panels are estimated to produce about 57% of ZCP’s energy demand.3

Contribution to community

Reducing carbon emissions in buildings has a crucial role in achieving the Paris climate goals and achieving net zero emission by 2050. An effective, efficient carbon neutral building takes cost-effective technologies in advantage to reduce emissions. It also serves as an lead example to improve health, equity, and economic prosperity in local communities. The action to invest in carbon neutral buildings around the world remains a priority and symbolises an important step taken in achieving sustainable development.

Bibliography

1 Peng, Changhai. “Calculation of a building’s life cycle carbon emissions based on Ecotect and building information modeling.” ScienceDirect, 20 Jan. 2016, www.sciencedirect.com/science/ article/abs/pii/S0959652615011695.

https://www.sciencedirect.com/science/article/abs/pii/S0959652615011695

2 Sikra, Sonya. “How Does Construction Impact the Environment?” Gocontractor, 21 June 2017,gocontractor.com/blog/how-does-construction-impact-the-environment/.

https://gocontractor.com/blog/how-does-construction-impact-the-environment/

3 CIC-ZCP. “Zero Carbon Park. Our Mission, Vision & Value.” CIC-Zero carbon park main webpage, zcp.cic.hk/eng/mission. https://zcp.cic.hk/eng/mission

4 “Modular Integrated Construction.” Buildings Department, 28 Oct. 2022, www.bd.gov.hk/en/resources/ codes-and-references/modular-integrated-construction/index.html#:~:text=Modular%20Integrated%20Construction%20(MiC)%20refers,for%20installation%20in%20a%20building.

https://www.bd.gov.hk/en/resources/codes-and-references/modular-integrated-construction/index.html#:~:text=Modular%20Integrated%20Construction%20(MiC)%20refers,for%20installation%20in%20a%20building.

5 Build King Contruction Ltd. “CIC Zero Carbon Park - emMiC (Stormwater Air Conditioning System).”

CIC Zero Carbon Park - emMiC (Stormwater Air Conditioning System), e-book ed., p. 1. Pdf.

6 Ashish. “How Does an Air Conditioner (AC) Work?” ScienceABC, 22 Jan. 2022, www.scienceabc.com/ innovation/air-conditioner-ac-work.html.

https://www.scienceabc.com/innovation/air-conditioner-ac-work.html

7 Richariya, Geetam, and Anil Kumar. “Solar cell technologies.” ScienceDirect, 2020, www.sciencedirect.com/topics/engineering/cadmium-telluride-solar-cell.

8 Amin, Nowshad, and Seyed Ahmad Shahahmadi. “Sustainable Energy Technologies & Sustainable Chemical Processes.” ScienceDirect, 2017, www.sciencedirect.com/topics/engineering/ cadmium-telluride-solar-cell.

9 “Cross Ventilation | Wind Effect Ventilation | Moffitt Corp.” Moffitt, www.moffittcorp.com/wind-effect-cross-ventilation/.

60 Scientific Harrovian 2022

Medicinal Applications of SPIDER SILK

by Jasmine Wong

Silk is a protein fibre spun by spiders to form webs for nests and cocoons, or to catch prey. Their unique properties, such as high toughness and extensibility, make them an excellent new biomaterial.

How is dragline silk naturally produced?

Each orb-weaving female spider has seven different glands, producing seven types of silk with unique properties depending on their purposes. The silk is stored as a liquid in the internal silk glands before it is secreted. It passes through the spigot to the spinnerets on the spider’s abdomen, where it is spun into fibre, forming gossamer [2, 18]. Among these seven different glands, the major ampullate (MA) silk is one of the spider’s most valuable silks, also known as dragline silk.

Mechanical Properties of Dragline Silk

The mechanical properties of dragline silk are affected by the amino acids present, insect size, diet, and body temperature [24]; the differences in mechanical properties are dictated by the type of secondary structure of the spider silk, which can be split into four different major motifs [9].

In summary, the primary structure of dragline silk is composed of a sequence of repetitive glycine and alanine blocks [25]. The chain of alanine is mainly found in the crystalline domains of the protein nanofibril composite as shown in Figure 2, whereas glycine is located in the amorphous matrix consisting of beta turns.

High Young’s modulus and tensile strength

The tensile strength (the greatest stress before breaking) of dragline silk is on par with the tensile strength of high-carbon steel (650 Mpa) [19]. The natural dragline silk produced by spiders can have a strength of up to four or five times that of steel. It has one of the highest breaking energies; hence, it is very tough and can withstand a large impact force without breaking [11]. Dragline silk also can undergo large tensile and compressive strains without fracturing or experiencing plastic deformation.

Dragline silk requires a large force of 1.1 x 109 Nm-2 to break under tension when stretched out at either end [9]. To put this into perspective, if you were to be stepped on by an average-sized African bush elephant that weighs 6,000 kg and has a foot size of 0.3 m2 , it would only exert an estimated 20,000 Nm-2 on you. A spider silk would require 55,000 elephants stacked on top of each other to break. If the silk is stretched to its yield point, some of the intermolecular interactions would break, causing the amorphous protein chains to extend, uncoil, and straighten out whilst keeping the polypeptide chain intact. As a result, it can be plastically elongated without losing strength under tensile stress – giving dragline silk its high tensile strength property. Furthermore, the combination of being able to withstand high stress yet experiencing little strain due to untangling of amorphous chains means spider silk has a high Young’s modulus value of 10 GPa. Young’s modulus is the stress-to-strain ratio, i.e., how much pressure will give a certain amount of deformation. This means it is very stiff and resistant to bending or stretching, due to hydrogen bonds breaking by a frictional stick-slip motion, in which energy is dissipated through the amorphous matrix.

Elasticity

The elastic properties of dragline silk further make it an excellent material. The extension of spider silk can be up to two to four times its original length, which is much longer than steel [11]. If an insect flies perpendicular to the silk, the web would need to absorb most of the kinetic energy of the insect’s forward velocity to bring it to a stop without causing the prey to be catapulted out of the web. The dragline silk can do this by transferring 65% of the kinetic energy to thermal energy and storing the rest as elastic deformation as it stretches and recoils back to its original shape and length. To do this, the silk must be extremely tough and extensible. Atomic force microscopy reveals that the silk contains a fibrillar structure with bleated fibrils at the fibre’s core. Bleated fibril is a section of fibre that has a completely non-repetitive random arrangement of loops. This core allows for a large force to be applied without breaking by extending itself,

Figure 1: The seven different types of silk produced by Spiders and the different shapes and properties of the silk shown in a diagram [14]

Figure 2: A diagram showing the composition of spider silk with a description of how it aids in causing the properties it possesses [8].

Figure 3: Molecular breakdown of the protein structure that makes up spider dragline silk [33]

as shown in Figure 4 below. Figure 4 also shows that dragline silk has a toughness of 160 MJm-3, meaning the silk can absorb a large amount of energy per unit volume and recoil after a force has been removed. This is because the surface crack propagates only up to a certain point in the crystallite [9] [24].

Dragline silk is fibroin and is made up of MaSp1 and MaSp2 Spidrion proteins which are composed of a repeating sequence of approximately 3,500 amino acids with 42% glycine and 25% alanine [6]. Glycine-rich regions give spider silk its elastic properties where a sequence of 5 amino acids is repeated. Unlike other amino acids, which have carbon instead, spider silk contains hydrogen as a side chain [3]. This is further enhanced by the fact that a β turn (180o) occurs periodically after each complete sequence, forming a β-spiral. Furthermore, the β spiral provides a tight helix which can extend with the amorphous area in the silk structure, providing elastic and tough properties. Its toughness is also brought about by the high molecular mass of the protein, causing many Van der Waal forces between the short-chain amino acids as well as the many hydrogen bonds between carbonyl and amide groups.

These forces are embedded in an amorphous glycine matrix consisting of helical and β-turn spiral structures. Additionally, the solid intermolecular forces of attraction between the layers of crystalline structure, i.e. disulfide bridges, give rise to elastic properties. Hence, when a force is applied, the silk is initially slightly stiff until the weak cross-links between the tangled chains are broken. The chains are then uncoiled, increasing strain for a little extra stress until the molecules become aligned. The band now becomes stiff as the strong covalent bonds between the atoms are stretched. On releasing the stress, the chains recoil back to their original structure.

The spring-like structure of the proline provides the corresponding restoring force to balance the torque acting on it [11]. β-turn is also neatly arranged to form a ‘cable-like structure’ which increases the crystalline stability and strengthens the spider silk. The elastic properties are further enhanced by the GPGXX region in the bleated fibrils where the hydrophobic crystalline structure is. This comes from having strong covalent bonds between every three amino acids in the helical structure, which further increase the tensile strength.

The fibre extensibility of the dragline silk compensates for strength when fibres are loaded on long silk, causing the web fibre to bend downwards, stretching the fibre with F=mg/2sinθ. Dragline silk is different from other low extensibility fibres: rather than the deflection angle becoming smaller, which will cause a larger force to develop, a larger angle allows for a higher εmax of 0.27. This is significant compared to the Kevlar fibre because even with a tenth of the normalised deformation, it will only support a load 40% less than the dragline silk. This is effective for spiders when catching insects flying at a high velocity.

Supercontraction

When submerged in water, spider silk fibres contract, causing a phenomenon known as a super contraction [11]. Changing humidity and moisture can cause the dragline silk to shrink by 40-50% and decrease stiffness by three orders of magnitude, causing it to behave like rubber. Supercontraction, therefore, keeps the web taut. This is believed to be the result of the polar acids forming bonds and interacting with neighbouring atoms.

Biocompatibility

The proteins in dragline silk are biocompatible to humans as they do not contain any toxic substances, nor do they cause immune rejection reactions from the human body. It was suggested in a study that silk produced by the common house spider, T. domestic, had bacteriostatic effects on B. subtilis [32] . The reasons for the reduction were suggested to be due to the copious amounts of glycoproteins in the silk. The hydrophobic nature of both the protein’s crystalline region and the GPGXX sequence can be degraded under specific conditions, and the degraded products can be absorbed by human tissue; hence it is an ideal wound suture and prosthesis-making material.

Glycine acts as an antioxidant, anti-inflammatory, and immunomodulator since it acts as a neurotransmitter in the central nervous system [4]. Being an immunomodulator means that it can change the immune system of the host by activating or suppressing it. Since spider silk is a natural material, it is cheaper and easier to use than manufactured materials. It has antimicrobial properties and is non-immunogenic, non-reactive and biodegradable. The response of mammalian cell lines cultured in vitro to Nephila clavipes further demonstrated that it did not evoke an autoimmune response [32].

Recombinant spider silk production

Harvesting a substantial amount of spider silk from natural sources is a difficult task; hence scientists have been able to produce recombinant spider silk to meet the demands [23]. To form a recombinant protein, recombinant DNA (rDNA) must first be formed. rDNA is a DNA strand that is formed by the combination of two or more DNA sequences from the same species. It can be artificially produced using rDNA technology to put into a host cell. The most common recombinant spider silk proteins are based on the sequence of Araneus diadematus. The most common host organisms used to manufacture the recombinant protein are E.coli, as they proliferate and have high cell density and easy transformation, i.e. high efficiency of introducing DNA molecules into cells and increased ability to express proteins.

Figure 4: A stress-strain graph comparing kevlar and spider dragline silk [29]

Figure 5: Graph of stress-strain to show the properties of Dragline silk, for example, toughness and stiffness

The formation of recombinant protein is as follows:

1. Restriction enzymes cut at a specific sequence of DNA to produce short, single-stranded overhangs[12].

2. Recombinant DNA is formed when the cut DNA fragment (target gene for the production of spider’s silk) is inserted into a vector (a plasmid) using DNA ligase.

3. The resulting vector is inserted into a host cell, ie. E.coli, in a process called transformation. This is done by shocking the bacterial cells with conditions such as high temperature to encourage them to take up foreign DNA.

4. The bacterial cells can now produce the recombinant protein.

5. Once the protein has been produced, the bacterial cells can be split open to release it.

6. The target protein must then be purified or separated from the other contents of the cells by biochemical techniques due to the presence of many other macromolecules around the bacteria besides the target protein.

Medical applications

Tissue engineering

Langer and Vacanti defined tissue engineering as ‘an interdisciplinary field which applies the principles of engineering and life sciences towards the development of biological substitutes that restore, maintain or improve tissue function’ to induce tissue-specific regeneration processes [5]. There are two approaches to tissue engineering. ‘Bottom-up’ is the modular assembly of building units into tissue resembling constructs [15]. ‘Top-down’ is the simple combination of existing components within a given structure.

Example 1: Silk Matrix for tissue-engineered anterior cruciate ligament (ACL)

The high tensile strength and Young’s modulus matches the mechanical properties needed for an ACL [1]. It is also a biocompatible material and avoids bioburdens associated with mammalian-derived materials. It also does not degrade quickly, which means it provides sufficient time for the host tissues to infiltrate and eventually grow back and stabilise the leg.

Example 2: Cardiac regeneration

The primary cause of impaired heart function is the loss of cardiomyocytes [10]. One innovative approach is to use spider silk to help grow new cardiac muscle tissue. By using bioengineered spider silk hydrogels as a base, scientists have been able to restore heart tissues. Cardiomyocytes, harvested from human-induced pluripotent stem cells (hiPSCs), are genetically modified using CRISPR/Cas-9 to allow the surface to be negatively charged, so that it can adhere to the positively charged bioengineered spider silk protein. This allows hypertrophy which repairs the sections of the heart. More importantly, the new cardiomyocytes also demonstrate the ability to communicate with other cells.

Prosthesis

An electro-tendon is a part of the robotic hand made up of spider silk which allows electrical signals to be transmitted to the pressure sensor by the transmission of electrical signals through to the pressure sensor, allowing the finger to bend under the control of a motor. It is able to do this as spider silk is a super tough conductor that can act as an electrode. The durable and flexible nature of spider silk allows the electrotendon to withstand up to 40,000 cycles of bending and stretching in a prosthesis hand [22].

Silk optics

Researchers from Taiwan have made biosensors using spider silk [20]. The dragline silk is harvested from Nephilia pilipes which is native and abundant in Taiwan. Spider silk forms the core of the optic fibres, whilst the biocompatible photocurable resin acts as the cladding. It is further enhanced by adding a nanolayer of gold to enhance the fibre’s sensitivity. In optomechanics, spider silk can be used to form sensors that can detect and measure tiny changes in the refractive index of a biological solution which contains glucose [30]. The beam produced is called a photonic nanojet (PNJ). This is useful as it can be used for biomedical nanoimaging applications, such as measuring blood sugar levels with a higher degree of accuracy without being invasive and expensive [20].

Sutures

Biotechnological spider silk production has enabled scientists to genetically modify the sequence of amino acids within the spider silk, thus altering the chemical and physical properties of spider silk proteins. With artificial spider silk, molecules like antibiotics and fluorescent dyes can be attached to desired soluble silk protein [13]. Antiseptic properties effectively clot blood because of its high vitamin K content. Hence, the rapid regeneration of biocompatible and multifunctional spider silk can have a wide range of applications that is useful for biomedical applications.

The point of sutures is to promote wound healing and avoid infections, but the suture itself is susceptible to causing bacterial infection of biofilms [11]. Thus, an extra layer of antibiotic-based antibacterial coating is added to the sutures to prevent bacterial biofilm formation. However, as microorganisms mutate and become resistant to antibiotics due to selection pressure causing evolution by natural selection, an alternative solution to this problem must be found. The biocompatibility, minimal immune response and controlled biodegradability make dragline silk most suitable for this role. Additionally, because spider silk can be easily degraded, it eliminates any changes or dressing removals that would typically be painful for the patient [7].

Conclusion

In conclusion, the dragline silk produced in the major ampullate gland in spiders provides a naturally high Young’s modulus, tensile strength, elasticity and extensibility. It is not only biocompatible and biodegradable, but it also does not evoke an immune response when used on other mammals, making it an attractive material for biomedical applications such as sutures and optic fibres.

However, the source of dragline silk production should be carefully considered, as exploiting spider glands is unethical since it is unnatural for them to keep making silk. In some cases, it is also inhumane to do so as they are involuntarily sedated with carbon dioxide gas and pinned down by their limbs and abdomen to keep them in place. Tweezers are then used to pull out silk from the spinnerets and attach it to the pool with some glue. The motor then begins to spin to harvest the silk from the spider [26].

Alternative methods should be found to avoid harming the spiders. This can be done by studying the structure of the spiders and using biomimicry to replicate the properties.

Figure 6: schematics of a prosthetic hand using spider’s silk [22]

Figure 7: The basics of a fibre optic cable [28]

[1] Altman, Gregory H., et al. “Silk matrix for tissue engineered anterior cruciate ligaments.” Science Direct, October 2002, https://www.sciencedirect.com/science/ article/abs/pii/S0142961202001564. Accessed 1 November 2022.

[2] Ault, Alicia. “Ask Smithsonian: How Do Spiders Make Their Webs?” Smithsonian Magazine, 3 December 2015, https://www.smithsonianmag.com/smithsonianinstitution/ask-smithsonian-how-do-spiders-make-webs-180957426/. Accessed 28 October 2022.

[3] Betts, M. J., and R. B. Russell. “Glycine: Amino acid properties and consequences of substitutions.” Russell Lab, M R Banes, 2003, http://www.russelllab.org/aas/ Gly.html. Accessed 28 October 2022.

[4] BYJU. “Glycine - Structure, Properties, Uses & Benefits with Images and FAQs.” Byju’s, https://byjus.com/chemistry/glycine-structure/. Accessed 28 October 2022.

[5] Campuzano, Santiago, and Andrew E. Pelling. “Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models.” Frontiers, 26 June 2017, https://www.frontiersin.org/articles/10.3389/fbioe.2017.00040/full. Accessed 1 November 2022.

[6] CHM BRIS. “Spider Silk.” Spider Silk, http://www.chm.bris.ac.uk/motm/spider/page3.htm. Accessed 28 October 2022.

[7] Cuffari, Benedette. “Role of Spider Silk in Biomedicine.” News Medical, 14 December 2020, https://www.news-medical.net/life-sciences/Role-of-Spider-Silk-inBiomedicine.aspx. Accessed 6 November 2022.

[8] Doistau, Benjamin, et al. “Recent Advances in Development of Functional Spider Silk-Based Hybrid Materials.” Frontiers, 29 May 2020, https://www. frontiersin.org/articles/10.3389/fchem.2020.00554/full. Accessed 12 November 2022.

[9] Ebrahimi, Davoud, et al. “Silk–Its Mysteries, How It Is Made, and How It Is Used.” NCBI, 24 August 2015, https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC4936833/. Accessed 29 October 2022.

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The Power of

STEM CELLS

by Jais Brar

As more research has been conducted in pursuit of new medical advances, stem cell therapy has emerged as a promising and hopeful treatment method for many conditions. In 2021 alone, the stem cell market was worth 77 billion HKD, and is continually growing at an exponential rate, it is estimated to surpass 246 billion HKD by 2030. (1) Stem cells can be used in numerous ways as they have the potential to develop into any cell found in the body. Unlike most cells that are only able to undergo a limited number of divisions before their death, stem cells can undergo an infinite number of divisions (2), making them one of the most unique scientific discoveries in the past 100 years.

This was followed by promising news, in 2012, stating that pluripotent stem cells could potentially be used to treat blindness. Human trials for this began in 2014, with Masayo Takahashi leading the study in treating age-related blindness and easing symptoms.(6) The inserted stem cells differentiated into retinal pigment epithelial cells, which are e damaged or lost in people with vision impairments, therefore improving vision and sight. Another way in which stem cells can be used in treating vision impairments is by collecting corneal limbal stem cells from a donor and using these to treat corneal damage. Although there are not cures for all of the sight related diseases, new remedies relating to optical issues such as glaucoma and wet macular degeneration, are being researched into extensively. (7)

Stem Cell Potencies

Stem cells all have the possibility of turning into specialized cells, however, within stem cells there are different levels of capabilities of transforming into different cell lineages. These include; totipotent, pluripotent, multipotent, oligopotent and unipotent, as shown in Figure 1.

The History of Stem Cells

Around 30 years ago, scientists discovered ways to obtain embryonic stem cells from early stage mice embryos. Biologists that studied these cells soon realized that the cells were pluripotent, meaning they have the potential to be converted into any adult body cell. Further laboratory experiments enabled scientists the ability to extract embryonic cells from humans and grow them in lab conditions. Prior to this, in the 1950s, the first stem cell transplant was given to nuclear researchers who had been exposed to radiation from cells found in the bone marrow. This procedure was carried out by Georges Mathé, a French oncologist.

Then later, in the 1960s, Ernest McCulloch and James Till gained new insight into blood cell formation through the discovery of haematopoietic stem cells. (3) This was done by injecting bone marrow cells into mice that had endured nuclear radiation. The cells were seen to develop into the three primary components of blood: red blood cells, white blood cells and platelets. Although these occurrences were rare,it demonstrated that differentiation was possible in bone marrow cells.(4)

Another major breakthrough in the stem cell world was the cloning of the infamous Dolly the sheep. Ian Wilmut and Alan Trounson, at Roslin Institute, managed to clone her using the DNA from an adult sheep’s mammary gland (found in the breast tissue), showing that if an adult cell was fused with an empty egg cell it would mirror the genetic makeup of the body it is being inserted into and replicate all tissues and organs, along with proving that the entire DNA of an adult was present in a single cell. (5) In around 1998, James Thomson and John Gearhart began to grow stem cells in the lab and in 2006, Shinya Yamanaka created induced pluripotent stem cells by injecting four key genes. Stem cells were increasingly used in medical therapy in the early 2000s, such as the first authorized trial on treating someone with a spinal cord injury with stem cells derived from embryos.

Totipotent Cells

Totipotency is the highest level of potency a stem cell can have. This means that they are able to differentiate into any cell, whether it be embryonic or adult. They can develop into over 200 different types of specialized cell in the body, making their differentiation potential optimal for medical use. Totipotent cells can be extracted from human zygotes, or zoospores, asexually reproductive structures found in algae and fungal species. The zygote is totipotent as it can evolve into any of the three germ layers; ectoderm (which forms the exoskeleton), the mesoderm (which forms the organs), and the endoderm (which forms the inner lining of organs).(9) Despite the fact that these cells fall into the most favorable category of stem cells, they are rarely used in scientific research as not only they are arduous to obtain but also go against various ethical guidelines. (10) As totipotent cells are derived from the first stage of formation of a fetus, obtaining them harms the blastocyst on the sixth or eighth day of development. This in turn destroys the embryo. However, as the embryos used in this practice are donated from IVF clinics and are deemed unwanted, it can be argued that it does not in fact breach any ethical regulations.

Figure 1 – shows the different potencies within stem cells (8)

After approximately 4 days, the zygote grows into an embryo. Embryonic stem cells are stem cells obtained from the inner cell mass of a blastocyst, which is a human embryo between 3 to 5 days old and contains about 150 cells only. Pluripotent cells can progress into any of the three germ layers, as shown in Figure 2, but not into any extra-embryonic structures, such as the placenta. These types of stem cells are completely pluripotent as they have the potential to be specialized into any body cell and even undergo mitosis, enabling them to divide into larger quantities of stem cells. This trait, along with being easier to acquire, allows them to be greatly useful for medical practices, especially in regenerating organs, tissues and aiding in overcoming a disease with limited treatment availabilities. (10)

Unipotent stem cells are characterized by their narrow capabilities in cell differentiation. They are only adequate for one singular cell lineage, for example muscle cells only being able to evolve into mature muscle cells. (13) Unipotent cells are distinguished from non-stem cells by a few key characteristics, one of which is being able to self-renew. (14) This is the process in which stem cells can divide and reproduce asexually with the help of mitosis, the cells self-divide in their undifferentiated states, which allow them to be highly beneficial. (15)

Stem cells can also be induced, meaning they can be created in lab conditions. Induced pluripotent stem cells (iPS) can be derived from adult body cells and have been reprogrammed through inducing genes to make them pluripotent. Like many other scientific advances, these cells were first found in mice fibroblasts (a lineage of cells that are responsible for the production of connective tissue) in 2006 by Yamanaka and then later in 2007 they were first independently produced from human fibroblasts. iPS cells behave in similar ways to embryonic stem cells and hold a lot of the same characteristics, some of which include expression of Embryonic Stem cell markers, chromatin methylation patterns (methylation inhibits gene expression in cells by affecting chromatin structure. Chromatin is a mixture of DNA and special proteins, such as histones) (16), embryoid body formation (three-dimensional aggregates) (17) , pluripotency and many more.

Somatic cells can be reprogrammed into iPS cells by the transcription genes Oct4 (octamer-binding transcription factor 4, a molecular marker for germ cell tumors) (18), Sox2 (SRY-box 2, a marker for multipotential neural stem cells) (19), Klf4 (kruppel-like transcription factor, a protein coding gene) (20) and c-Myc (MYC proto-oncogene, BHLH transcription factor, a regulator of cellular metabolism and proliferation) (21). These factors, along with a few others,can reprogram adult somatic cells (any body cell that is not a gamete) and transdifferentiate them into neural stem cell like structures (22). iPS cells can be an excellent alternative to embryonic stem cells as they are comparatively less invasive, making them more ethical. They can also be especially useful in regenerative medicine (involved with regenerating tissues or organs), disease modeling and drug discovery. (23)

As mentioned previously, the most prominent attribute of stem cells is that they are able to differentiate into any desired cell. When a cell divides by mitosis, it forms two identical daughter cells and these cells can either: both remain as stem cells, both differentiate into new cells or have one remaining as a stem cell and the other differentiating . When both daughter cells either differentiate or remain as stem cells, it is called a symmetric division, whereas when they both carry out different processes this is known as asymmetric division. The chances of a symmetric division happening, 70%, is relatively high compared to those of an asymmetric division, 30%. This property allows the cells to retain their ability to perpetually divide as it ensures that stem cell levels are kept at a constant level, i.e. stem cells don’t deplete.

These types of cells have a lower differentiation potential compared to pluripotent cells. Multipotent cells are limited in their capacities, they can specialize into sub-cells in a specific cell lineage but cannot develop into any type of cell. An example of multipotent cells are hematopoietic cells, which can be found in bone marrow or in the blood from the umbilical cord. Hematopoietic cells have the ability to evolve into any blood cell but are unable to produce cells that are not blood cells. In recent years, scientists have located the presence of multipotent hematopoietic cells in the heart, which have the tendencies to develop into heart muscle of endothelial cells. These can be extremely helpful in treating blood cancers like leukemia. (12) Oligopotent cells, found within specific tissue e.g. the cornea , can self-renew and regenerate into more lineages within a particular type of cell. They can also form terminally differentiated cells of a specific tissue, meaning oligopotent cells no longer have the ability to undergo mitosis and proliferate. (13)

When it comes to the mechanics behind the specialization of stem cells scientists are still unsure as to what aids it since they are still relatively new. Producing mature neurons is pivotal to understanding the physiology of human neurons and glial cells and the pathology of neurological diseases, such as epilepsy. The cells differentiate into neural progenitor cells by embryoid body formation, then they are directed into specific neurons. These steps are all accomplished with the help of transcription factors.

Pancreatic β-cell helps in glucoregulation, when blood glucose levels are too high they produce insulin therefore the production and transplantation of these β-cells can treat diabetic patients. For this cells are induced into a definitive endoderm (one of the three germ layers) and then they further differentiate into pancreatic cells. (24) Pluripotent stem (iPS) cells can also be used in myogenic regeneration of skeletal muscle and cardiac muscle, along with hepatocyte differentiation (hepatocytes are parenchymal cells in the liver that are crucial in metabolic action, detoxification and protein synthesis) (25).

Figure 2 –This shows the three germ layers that an embryonic stem cell or other pluripotent stem cells can specialize into. (11)

Medicinal application of stem cells

Since stem cells are so versatile, they can be used profusely in treating medical conditions. Some of the conditions include:

Tissue regeneration:

Prior to the discovery of pluripotent stem cells, patients with damaged organs or tissues had to wait extensive periods to receive a transplant but in present times scientists can use cell differentiation to grow organs and tissues to replace the organ.(26)The human skin has remarkable regenerative capabilities, especially with the epidermis (the outermost layer of skin) being able to continually regenerate. This is most helpful when treating severe burns and other chronic wounds. Plastic surgeons use stem cells extracted from beneath the skin surface to grow new skin tissue. This newly grown skin tissue is placed onto the open wound, allowing the skin to grow back, closing any exposed wounds. (27)

Cardiovascular disease treatment:

With ischemic heart disease being the leading cause of death in the world, it is essential that there are successful therapies to prevent myocardial infarctions (heart attacks). Scientists have found methods to insert stem cells into the cardiac tissue with a catheter to help regenerate the deteriorated tissue, improving the patient’s quality of life. (28)

Brain disease treatment:

Stem cells can be used to replace and regenerate impaired brain cells that cause neurological disorders, such as Parkinson’s and Alzheimer’s. Parkinson’s disease, for example, is caused by lowered levels of dopamine in the brain due to a loss of nerve cells in the substantia nigra (located within the midbrain).

(29) Stem cells can be directly placed in the brain where the damaged nerve cells are, where they regenerate into nerve cells and regulate dopamine levels, suppressing certain symptoms of the disease. Although this is not a definite cure for the disease it can help lessen the symptoms, and hopefully with more development can act as a permanent cure. (30)

Blood disease treatments:

Blood diseases, such as leukemia, multiple myeloma and lymphoma, can be a consequence of genetics, side effects of medication or due to a lack of particular nutrients. (31) The bone marrow produces all blood cells, thus by taking hematopoietic stem cells from the bone marrow or the umbilical cord can produce healthy red blood cells to carry oxygen and healthy white blood cells to fight the cancerous cells, infections and other pathogens. (32) In cases of hemophilia A, a blood disease caused by the lack of blood clotting factor VIII that causes excessive bleeding as the blood isn’t able to clot. Stem cells can differentiate into platelets to aid in blood clotting as a treatment for the disease. (33)

Conclusion

In conclusion, stem cells are exceedingly beneficial to the medical world due to their versatility. Although their use is controversial as they are derived from living organisms and can be seen as wasteful, the amount of effort and money that goes into the research and advancement of stem cells will in turn change the way we perceive them, and reveal how valuable stem cells are to humans.

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