Laureates of Mustafa (pbuh) Prize 2019

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A Warrior in the ‘Valley of Death’

To fight a tricky disease such as cancer, you need a weapon at least as tricky

Some time ago there was a debate in media about if physician-scientist is an endangered species or a new species evolving through hybridization. A physician-scientist, an effective bridge between these two worlds, is a physician who is doing some forms of basic science research to solve clinical problems.

The importance of this kind of research in medicine is not just academic. In a sense, physician-scientists ‘translate’ practicing physicians’ language into research scientists’ one, and vice versa. Thus they play a critical role in so-called translational medicine, or as sometimes called, bench (laboratory) to bedside (clinic).

If a doctor is supposed to be committed to do everything possible to save his patient, it may not suffice just to order from the menu, prescribing whatever drugs are available and using whatever tools already developed; It may sometimes means going back to laboratory and doing some basic biomedical research to find a new medicine or invent a clinically effective tool.

The Valley of Death

Can an eminent scientist be an eminent physician too? Well, yes, but it’s not something you see every day. Currently, there is a chronic severe, even growing, shortage of physician-scientist at the global level – only about 2 percent of the total number of doctors in the US. “Translation as such is not taught in any university program, it is something that you learn by being involved with interdisciplinary research teams,” says Ugur Sahin, Professor for Translational Oncology and Immunology and Managing Director of Science and Research at Translational Oncology (TRON) biopharmaceutical research organization.

TRON, founded in 2010 with the initial financial support of €30 million, situated in a newly built research building on the campus of the Medical Center of the Johannes Gutenberg University in Mainz, Germany. As it has been stated on the webpage of the organization, TRON “pursues new diagnostics and drugs for the treatment of cancer and other severe diseases.” It defines its mission as putting inspiration into practice to find viable solutions for challenges and translating scientific insight into clinical practice.

Translational medicine is an interdisciplinary approach and needs overlapping expertise. Physician-scientists have formally trained both as a medical practitioner and as a scientific researcher; hence they have an M.D. and a Ph.D., usually in biological sciences. The main difference between a physician-scientist and a typical biomedical researcher is in the firsthand intimate experience the former has with the patient that could be used to guide research in the lab.

However, teamwork doesn’t take place automatically. As they say, ‘getting good players is easy, but getting them to play together is the hard part.’ This is not an easy challenge “to form a team of interdisciplinary scientists, as it takes time for such a diverse group to function smoothly,” says Sahin.

TRON tries to explain why this new approach is dramatically different from the traditional one: “Historically, the pharmaceutical industry carried discoveries from basic research into clinical trials; recent developments have effected a dramatic change in this process. The basic and clinical research sectors have as a result diverged and the emerging gap is considered ‘the valley of death’ in translational research.”

One of the ugliest demons in this ‘valley of death’ is cancer, undoubtedly. “The treatment of choice for some forms of cancer has hardly changed for decades, so new clinical solutions are needed as soon as possible,” Shain says. There are two research departments at TRON, both of them pursuing promising methods to treat cancer, though by different approaches: The Biomarker Development Centre searches for clinical biomarkers or state indicators of each particular kind of cancer, and the Immunotherapy Development Centre is after beating cancer using the human immune system.

A Crazy Idea

Using the immune system to tackle cancer - or cancer immunotherapy - considered a ‘crazy idea’ from the beginning. Sahin and his wife, Özlem Türeci, both born to Turkish immigrant families in Germany, were thinking about cancer vaccines when they were medical students at Johannes Gutenberg University in Mainz in the early 1990s.

“There is huge medical need. Each year about 10 million patients die due to cancer. My research focusses on immunotherapy. We are developing cancer therapies such as vaccines and antibodies to inform and enable the patient’s immune system to attack cancer cells,” Sahin explains.

The logic is simple: No two patients have exactly the same genetic mutations in their cancerous cells and thus each patient’s treatment should be individualized. The only system capable of adapting is the immune system. Therefore, it is the immune system that should be used as a defense. Bingo!

Unfortunately, translating this idea into reality and recruiting the immune system to fight cancer in practice is not as simple as it may seem. Three decades ago, most pharmaceutical companies considered the idea of cancer vaccines crazy and refused even considering immunotherapy concepts.

Sahin, the recipient of the 2019 Mustafa  Prize for ‘development and clinical testing of cancer therapeutic vaccines based on the mRNA for the individual patients regarding their mutation profile,’ says “my research is about empowering the patient´s immune system to fight cancer and other diseases.”

According to Sahin, the greatest challenge for the treatment of cancer is that every patient has a different type of cancer. Even within one patient, there are billions of cancer cells that are all different. The current way of how cancer is treated ignores this challenge. That is the reason why usually only 20-30% of patients with cancer respond to therapy.

“The key question of my research is how we can develop cancer therapies that acknowledge and address the challenge. My research has led to the development of individually tailored cancer immunotherapies. That means we analyze the individual cancer of the patient, we identify the unique features of the patient´s cancer and make a vaccine which is individually tailored. That means every patient gets a unique therapy,” he says.

To create cancer immunity, you should direct T cells - a type of lymphocyte which plays a critical role in the body’s immune response – to attack new proteins expressed by mutated genes on the surface of cancerous cells. However, spontaneous immune recognition of such mutations is too late and too insufficient.

The ingenious solution of Sahin and his team is the personalized vaccines that train the body’s T-cells to attack tumors. They use synthetic mRNA and code it to include all the necessary information to tell T-cells what proteins to make. This engineered mRNA enables them to identify uniquely mutated proteins on the surface of an individual’s tumor cells and mobilizes immunity against a spectrum of cancer mutations.

However, this would work only if you can find any unique mutation not found elsewhere in the body. The process of finding the mutations and putting them in mRNA has facilitated and accelerated through faster computing and gene sequencing technology.

The Spirit of a Warrior

In 2017, Nature published a pair of curious papers showing the efficacy of the treatment. Both studies have applied the concept for the first time on human. One of them has been conducted by BioNTech, a biotechnology company pioneering individualized immunotherapies founded in 2008, of which Ugur Sahin is Chief Executive Officer. Sahin and his co-authors showed the vaccine has stopped the spread of melanoma or skin cancer and shrink tumors in five patients.

“Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer,” they write. It seems that mRNA-based cancer immunotherapies and vaccines are entering clinical utilization: A true case of the bench to bedside studies.

In the past couple of years, many drug companies were eager to invest in this novel genetic information delivery method and the potential new drug class that may result from it. Cancer vaccines, however, are still unproven and many such efforts in the past boiled down to nothing but another spark of hope died and added to the long list of failed attempts. Nevertheless, to fight a tricky complicated disease such as cancer, you need a weapon at least as tricky and complicated, and of course, the spirit of a warrior.

enlightenedProfessor Sahin's photos in the 2019 Mustafa Prize award ceremony and the 6th Science and Technology Exchange Program (STEP) held by the Mustafa Science and Technology Foundation (MSTF) are available here:

http://mustafaprize.org/media/?id=4056

The warrior who brought COVID-19 to its knee

In November 2020, amid the world’s desperate struggle against the novel Coronavirus, it was announced that the COVID-19 vaccine developed by Ugur Sahin was found to be 90% effective.

The New York Times:

Lauding Ugur Sahin’s remarkable achievement in fighting the deadly COVID-19 pandemic, The New York Times wrote: In 2019, Dr. Sahin was awarded the Mustafa Prize, a biennial prize for Muslims in science and technology.

https://www.nytimes.com/2020/11/10/business/biontech-covid-vaccine.html

Deutsche Welle:

“BioNTech: Moving at the speed of light toward the first Corona vaccine”

DW published a report on Ugur Sahin’s success in developing a COVID-19 vaccine with 90% efficacy, highlighting a part of his Mustafa Prize acceptance speech: “‘I realized very early that I was interested in science,’ said Sahin on the occasion of the 2019 Mustafa Prize.”

https://www.dw.com/de/biontech-mit-lichtgeschwindigkeit-zum-ersten-corona-impfstoff/a-55472126

With the announcement of this COVID-19 vaccine’s high efficacy, DW’s Arabic-language television channel commenting on Ugur Sahin’s being selected as a 2019 Mustafa Prize laureate, said: “It is safe to say that Mustafa Prize commended Ugur Sahin’s achievements prior to any other scientific institution.”

Indonesian Media:

“‘Muslim Nobel Prize’ and COVID-19 vaccine”

Sahin’s success in developing a 90% efficacious COVID-19 vaccine received widespread media coverage in Indonesia.

Elaborating at length on how this mRNA vaccine works, Kompas noted that Sahin’s outstanding achievement in the area of mRNA technology that brought him the 2019 Mustafa Prize, is now regarded as the glimmer of hope for putting an end to COVID-19 pandemic.

The Mustafa Prize, “an award that the Science Journal called ‘the Nobel Prize for Muslims,’” announced five winners in 2019 among which was Ugur Sahin—a 55-year-old Turkish scientist who has completed his academic career in Germany, wrote Kompas and Republika.

Referring to the 2019 Mustafa Prize award ceremony, Republika wrote: In November 2019, an event was held which was attended by representatives from at least 30 countries of the Organisation of Islamic Cooperation (OIC). “This time it was not politicians, but scientists” from hundreds of research institutes gathered under one roof.

https://republika.co.id/berita/qjla20393/nobel-muslim-dan-vaksin-covid

https://bebas.kompas.id/baca/bebas-akses/2020/11/12/kolaborasi-vaksin-covid-19-biontech-pfizer-melampaui-rivalitas-seribu-tahun/

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Changing the World

Ali khademhosseini; An Intimate Profile

For a bioengineering researcher, no paradise could be imagined as more welcoming than a lab on the ‘bridge’ between a medical school and an engineering school in one of the most pioneering universities in the world. Just here, at this strategic bridge, lies Khademhosseini Lab at UCLA. “Our research really bridges the two and this is one of the things I’m very excited about,” says Ali Khademhosseini, the Levi Knight Professor of Bioengineering, Chemical Engineering and Radiology at the University of California-Los Angeles (UCLA).

Ali Khademhosseini was born on October 30, 1975, in Tehran. “I recall that my brother and I grew up in a loving family. Our parents always encouraged us to do well and be the best we can be. I think that both my parents have helped me in having the important values in life,” he says.

Then everything changed with the advent of the war between Iran and Iraq in 1980 when he was only five. “I remember vividly one time we were sitting down and there was a mushroom cloud that went up a few blocks from where we were that one of the rockets had hit it. So obviously it’s some experiences that you never forget but at the same time, it makes you appreciate the opportunities that you have in the US right now,” he says.

He liked playing video games and reading at home, as well as outdoor sports. Math and science was his favorite subject in school. At various times he wanted to have different careers like a professional athlete, chess player, high school teacher. Later on, however, when he went to university and found his passion for research he became interested in becoming a professor.

“I was always interested in seeing how the world works and the fundamental laws that govern it. I used to watch a lot of documentaries about nature, science, and technology. I think that despite this my passion did not really get ignited until I was in the third year of university and got my first research experience,” he says.

During the summer of his third year studying chemical engineering at the University of Toronto, he had the opportunity to get involved in undergraduate research in the area of biomaterials, under Dr. Michael Sefton. He found it fascinating to see the engineering knowledge that he had been studying at the university become useful in solving important medical problems.

After getting his Master’s at the University of Toronto (2001), he was accepted as a Ph.D. student at MIT. There he met and inspired by Dr. Robert Langer, one of the twelve Institute [= distinguished] Professors of MIT, and a world-renowned figures in biomedical engineering innovation. “Professor Robert Langer showed me that there are no boundaries in what an individual can achieve. He was really important in my professional development,” he says. “You see the humility and kindness of the person towards people he interacts with. It really does change your mind. It still motivates me, pushes me forward.” He received his Ph.D. in bioengineering from MIT in 2005, with Dr. Langer as his doctoral adviser.

The other mentor Khademhosseini recalls of having a great effect is Nicholas Peppas of the University of Texas at Austin who “has been very influential and helpful” and helped him to improve his “critical thinking and managing academic life.”

Khademhosseini was a professor at Harvard Medical School and a director at Biomaterials Innovation Research Center (BIRC), a leading initiative in constructing engineered biomedical materials. Then he joined the Division of Health Sciences and Technology, which is one of the largest academic collaboration between Harvard and MIT in the last half-century. From Nov. 2017 he joined UCLA and is the founding director of the Center for Minimally Invasive Therapeutics at UCLA.

Khademhosseini is trying to develop various types of diagnostic and therapeutic strategies by merging engineering and medicine. For example, his team develops ways of engineering artificial tissues using advances in stem cell biology, 3D printing, and materials science. “Our research can make great impact in medicine by making long-lasting therapeutics that can benefit the patient for many different types of diseases, ranging from cancer to trauma and organ failure due to old age,” he says. “Our work has the potential to change medical practice.”

He is an author in more than 600 scientific paper and book chapter which have been cited more than 55,000 times so far (75% of them in the last 5 years) and brought him an H-index of 123. Khademhosseini was selected by Thomson Reuters as one of The World’s Most Influential Minds and was a regular name in the Web of Science list of Highly Cited Researchers in the past few years. This list recognizes researchers producing publications that rank in the top 1% of the most cited. He is also on the editorial boards of many journals with high impact factor among them are ACS Nano, Small, Biofabrication, Lab on a Chip, and Biomacromolecules.

He is a recipient of more than 40 major national and international awards, including the 2011 Presidential Early Career Award for Scientists and Engineers (PECASE), and a fellow of many learned societies, both domestic and abroad, including American Association for the Advancement of Science (AAAS) and Royal Society of Chemistry (RSC).

Khademhosseini is a family man. “When I am at home I like to play games with my son and teach him things. I love spending time with my son! Also, I like to spend time with friends. My wife is also very supportive and we try to go out in the sun of Los Angeles or drive around California,” he says.

He likes to be known and recalled as a good mentor as well. “I really care for everyone who is in contact with me and try to make sure that they have a good life.” Many of his former students and postdoctoral fellows now work as successful researchers in the most prestigious universities in the world. This is why he received the title of MIT’s Outstanding Undergraduate mentor.

Many students interested to work with Khademhosseini, especially from Iran and other Middle Eastern countries, are rushing into his lab. “I always see myself as one of those people who could have been applying to my lab. My main advice to any student is that first to explore different things and find your passion,” he says. Khademhosseini believes that a researcher should believe that he or she is solving important things. “You’re not just doing something that keeps you busy like solving a puzzle that at the end no one cares about. If you actually do your work then you can make a big impact, you can change the world,” he thinks.  

Printing Spare Life

Biofabrication may be a little bit off in the future, but it still seems the future of medicine

Biofabrication seems like a word embodied all the good dreams of both a transplant patient and a bioengineer. If your kidneys are failed, would you like two new ones to be printed for you? If there is no histocompatible lung available for your terminally sick patient, would you like to print a new pair for her using her own cells? Does it like an extreme case of science gone magic?

The tissues and organs of living things are the result of the genetically programed developmental processes that evolved for a long time. Now biofabrication seems an artificial alternative to make tissues and even whole organs: Life 2.0. And you need life 2.0 most urgently when the life 1.0 has failed – a sort of life after life.

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The world population is going to age in the coming decades and it is estimated that the number of people aged 65 and older would be doubled by 2050 and constitute one-sixth of the whole population. Current treatments, such as joint replacement and organ transplantation, suffer from infections, tumor malignancies, immunosuppression necessity, and supply shortage. 3D constructs and other regenerative therapeutics provide a reliable option of minimally invasive surgeries to address their organs' natural deterioration.

Print or Perish

The basic principle is called additive manufacturing or printing a concoction of cells, fibers, and gel, layer on layer. Thus the 3D printing technology has a central role in biofabrication as a powerful tool to accurately put cells into a matrix.

Many tissues consist of several types of cells. So it is very desirable to print all of them together instead of using stem cells and waiting for them to differentiate. These printed tissues then are hoped to reorganize and remodel themselves to a fully matured and interconnected structure.

Currently the list of constructs, or things that can be printed using this bioink, is long and includes a range of tissues like skin, tendons, cartilage, bone, blood vessels, nervous, the pancreas islet cells, trachea, as well as whole organs such as kidneys, bladder, liver, lung, heart and more.

These tissues and organs can be used both for treatment and for research: They could be used as a substitute in the medically challenged and replace the damaged ones. And they could be used as a realistic model to test new drugs, and discovering the cellular biology mechanisms while reducing animal use in research.

Bones of Contention

The bioink using in the three-dimensional bioprinting is indeed a cell-laden biomaterial fed into the printer. For example, those used for bone bioprinting are hydrogels bearing cells, bioactive ceramics, and growth factors, which should be stable at normal body temperature. Hydrogels are indeed hydrophilic networks of polymers like collagen or polysaccharides that turn into a gel when hydrated (over 90% water). The hydrogels are basically like a natural tissue devoid of all its cells. To give them a rigid three-dimensional shape and mimic a natural tissue scaffold, researchers use cross-link nanofibers. And they act as a medium to manage cells by adding biosignaling molecules.

The most common hydrogel in bioprinting is alginate, or salts of alginic acid, which is a polysaccharide isolated from brown algae. Alginate forms a viscous porous gum when hydrated and is the most frequently used biomaterial due to its low cost and biocompatible nature. Another biomaterial that is being investigated as bioink is silk fibroin which is derived from both silkworm and spider silk.

What are printed by 3D technology are scaffolds that then could be seeded by the respective tissue cells. Now the 3D bioprinting takes a further step and use bioink containing cells and bioactive cues and have many advantages over ‘traditional’ two-step printing.

Bones are a most demanded tissue in transplant surgeries. They may defect because of many factors such as congenital abnormalities, trauma, disease, or surgical resection. Bone grafts to restore structure and function come usually from the same person’s body (autografts) or are donated by another person (allografts), and as they must be healthy, they should be considered as a limited resource. And synthetic biomaterials just will not do the work properly. After all, bones are complex living tissues with blood vessels and using this technology in clinical settings could be accompanied with complications not least among them the immune reaction or lacking the right mechanical properties or the potential to fuse in the recipient sites.

Off in the Future

Considering all these formidable challenges, it is not surprising that 3D printing is one of the cutting edges in the fast-advancing research area of regenerative medicine. Developing complex custom-made constructs for personalized regenerative treatment has recently ignited much research interest.

Much of what said above and many more are in the realm of Ali Khademhosseini, bioengineering professor and director of the Center for Minimally Invasive Therapeutics at the University of California-Los Angeles (UCLA). He, as a world-leading expert in tissue engineering, concedes that currently, the main use of bioprinting is in vitro - by reducing the number of failed drugs. This makes it possible to test different drugs on patient genetically unique tissues outside of his body before prescribing medicine for him.

Khademhosseini, the laureate of the 2019 Mustafa Prize for ‘nano- and microfabricated hydrogels for biomedical applications,’ accepts that much of being dreamed of in the field of bioprinting, especially in the form of transplantation by putting cells in a printed architecture and converting it to a living functioning tissue, is “still a little bit off in the future.” In the future, we should be able to custom-made tissues and organs for each person using his or her own genomic data.

These kinds of testing are now underway and the results are being fed to machine learning algorithms to improve predictiveness. The challenges are vast and various, however, “I’m sure with time we’ll be able to solve all of them,” said Khademhosseini in an interview with UCLA Samueli School of Engineering. A host of Middle-Easterner researchers currently are working on similar subjects in the most prestigious universities, such as UCLA and Harvard Medical School.

All of this bioprinting issue reminds many of the Westworld, a TV series based on a 1973 work written by Michael Crichton. The opener shows two 3D printers working simultaneously to extrude out of their nozzles the final touches of the skeletomuscular and vascular systems and finally skin of ultra-realistic robotic hosts of an amusement theme park along with their horses and guns. However, many academic labs throughout the world are busy researching and developing any aspect of this concept intensively. Many of those fictions will become proper science soon.

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Lightning Whisperer

Ümran Savaş İnan; An Intimate Profile

After the midnight of 15 September 2001, Ümran Inan, then a professor of electrical engineering at Stanford University, and his colleagues recorded an astonishing lightning event above thunderstorm cells had clustered 200 kilometers away from their observation site. About a decade earlier, the first case of such events was captured by a camera. So they were waiting for some bizarre kinds of electrical discharges but what they witnessed was beyond their expectation. The event was apparently an upwards lightning, called “blue jet”, but in this case the jet just propagated to the altitude of about 70 km, roughly twice as the upper limit of normal blue jets were observed before.

That night, Inan and his colleagues, In fact, discovered a new type of electrical discharges now known as “gigantic jets”. In their report of the event that published in nature, they noted: “as we observed this phenomenon above a relatively small thunderstorm cell, we speculate that it may be common.” But it turned out that it is not, the gigantic jets are so rare that only about a dozen of them have been observed since then.

Not so Engineer

Ümran Savaş İnan, born in Erzincan, Turkey (1950), emeritus professor of electrical engineering at Stanford University, is internationally recognized as a leading researcher in the study of upper-atmospheric phenomena. Despite his background in electrical engineering for Bachelor’s (1972) and Master’s Degrees (1973) at the Middle East Technical University in Ankara, many of his most cited papers are in the field of near-Earth space physics. When he went to Stanford University for a Ph.D. scholarship, he realized that his research group was working on topics that had much more to do with atmospheric and space physics than engineering. “I was first worried about the fact that this field was too specialized, especially when I return to Turkey,” he says.

In the following, he became interested in the physics and chemistry of the upper atmosphere and while he could switch to any other research group in the electrical engineering department, he stayed in a field that was entirely new and challenging for him. “Because of my deep education from Turkey, my inherent interest in the topic, and because I prefer to be challenged rather than take the easy path, I thus decided to stay,” he says.

However, the decision might have rooted in his childhood. Inan’s father was head of the forecast division of the Turkish Meteorological Service, and obviously Inan, as a kid, might have a tighter bond to atmospheric affairs including lightning than any other kids. His father's job as a public servant also affected his future profession in another way. He was an outdoor-oriented child and used to play soccer and volleyball in their neighborhood along with his two brothers. Every time there was a government change, his father would be worried about being assigned to a new city. Because of those unpleasant movements, Inan didn’t want to work for government, or even in private industry. “At the beginning of high-school, I decided to be an academician. It looked to be the profession in which I could also be my own boss,” he says.

Inan’s decision to be an academician was not just a matter of job preference, he wanted to pursue science, even as a teenager. He was such an eager reader who wouldn’t pass out any text, even those on wrappings or bags made of obsolete newspapers. And, his interest in science grew out of his curiosity and passion for reading. As a regular visitor of the British and the American Libraries in Ankara, when he somehow ran into books about chemistry and physics, he got so obsessed that he decided to set up his own science lab. “I used all my allowance to buy chemistry equipment and actually conduct some dangerous experiment and set up my own laboratory in the balcony of our house,” he recalls.

Good fellows

After receiving Ph.D. degree in Electrical Engineering from Stanford University in 1977, he joined the staff of the faculty as a research affiliate and in 1982 was appointed as an assistant professor in the Department of Electrical Engineering. He became an associate professor in 1985 and receiving the professor title at Stanford University in 1992. During 1997-2010, Inan has served as Director of the Space, Telecommunications and Radioscience (STAR) Laboratory.

Inan has authored or co-authored more than 360 scientific publications. Some of his highly cited papers co-authored by Timothy Bell, his Associate Advisor at Stanford University, who along with Robert Helliwell (1920-2011), his Ph.D. Advisor Professor, were the most influential persons in his scientific career. “I learned so much from both of them. As I became a faculty member and became the Head of our Research Group, it was my turn to mentor both of them and create a fruitful and enjoyable scientific environment for them and our many students,” he says.

After many brilliant years at Stanford University, Inan has begun another professional experience as the President of Koç University in Turkey, since 2009. He says there are some open questions in his field of research that are important on a planetary scale, including “Whether the Earth’s radiation belts would be significantly different if there was no lightning activity in the lower atmosphere?” But he doesn’t have any plans to do further research in this area. However, he doesn’t seem worried about his scientific legacy: “I am pleased to indicate that 15 of the Ph.D. students that I graduated are academics at various universities and they will be pursuing these questions and others, which are still open.”

Inan served as the Principal Ph.D. Dissertation Advisor for 60 students who graduated since 1990. “My career was also greatly influenced by the 60 Ph.D. students whom I supervised,” he says. He considers the successful graduation of these many bright students and friends as “the most important achievement of my career, much more than any papers I have written or scientific talks I have presented.”

He believes the most important of life is integrity in everything that one does and sincerity in dealing with other people. “Genuine friendships and collegiality (friendly cooperation) between people are the most important aspects of life, since at the end of a career, the only things that matter are these friendships and the memories of the good things that you have done with and for people.”

What’s going on up there?

Discovery of lightning between earth and space sent scientists back to the blackboard

A downward progressive flashing crack in the sky and a tremendous sound, a few seconds later. As far as it may concern to most of us this is a perfect definition for lightning, a familiar atmospheric phenomenon that may happen about 50 times per second, or 4 million times a day, across the world. But if you ask the experts, they will tell you that despite centuries of scientific scrutiny and a lot of findings, lightning has remained a strange mystery.

Throughout history, lightning has both fascinated and frightened people by its splendor and might. Ancient Greeks, for example, associated it with Zeus, their most mighty god. However, early scientific experiments on lightening in the mid-18th century, including Benjamin Franklin’s famous experiment with a kite, deciphered the electrical nature of lightning. Even after a modern understanding of lightning developed, the phenomenon continued to amazed lucky observers.

For more than a century, especially after the dawn of aviation, there have been lots of reports describing unusual luminous displays flickering through the upper layers of the sky. Although many of them could be explained by auroras or some kind of strangely illuminated clouds, in certain cases particularly those occasionally observed by pilots during flights above thunderstorms in the night sky, were quite baffling. According to the reports, lightning could happen in strange forms, colors, orientations, and locations.

Seeing is Believing

Until the late 20th century, the scientific community mostly regarded such reports as apocryphal. But in 1990, when John R. Winckler and his colleagues at the University of Minnesota captured one of those enigmatic phantoms using a video camera for the first time, it turned out that there are varieties of lightning of completely new configurations. Winckler’s achievements led to flourishing a whole new activity to record and document these high altitude electrical phenomena. Since then, many strange forms of lightning, from long blue pillar to giant red jellyfish, are discovered.

By the end of the 1990s, it turned out that lightning-like phenomena are not restricted to the low altitude sandwiched between thunderclouds and the ground. In fact, electrical discharges could take place in a wide range of altitudes, from lower atmospheric layers up to 100 kilometers above thunderclouds.

These luminous events, many of which are visible to the naked eye, surprisingly remained undiscovered for so long. Even more surprisingly, way before observing these events, scientists knew some form of lightning could happen high in the atmosphere. They have long known that in higher altitudes where the atmosphere is far less turbulent, ultraviolet rays from the sun cause the gas molecules to lose electrons. This is the process that creates the ionosphere, the electrically conductive envelope around the earth.

Large differences in voltage can exist between storm clouds and the ionosphere, just as they do between clouds and the ground. But what happens in the upper layers is different from what we usually observe as typical lightning strikes to the ground. The density of atmosphere decreases by increasing altitude so the lightning that happens at higher altitudes involves fewer air molecules and creates different shapes and colors.

The revelation

TLE (Transient Luminous Event) which is the more accurate term for upper-atmospheric lightning falls into four categories: red sprites, elves, blue jets, and gamma-ray events. Despite their fanciful names, scientists have made considerable progress in understanding theses ghostly atmospheric events. One of the pioneering researchers in this field is Umran S. Inan, emeritus professor at Stanford University and the president of Koç University in Turkey, who has a remarkable contribution to theorizing the underlying physics of the TLEs.

Inan, one of the laureates of the 2019 Mustafa Prize from Islamic Countries, and his colleagues at Stanford University were particularly at the forefront of the discovery of red sprites and elves. “The observation of these very common but sub-visual luminous phenomena at altitudes ranging from 50 to 100 km was a surprising discovery in the mid-1990s”, Inan says, but much of the underlying physics and properties of these phenomena were extensively modeled and measured by the works of himself and his many doctoral students.

In 1995, one of the first major theories to explain red sprites and elves was proposed in a paper by Inan, Victor Pasko, his doctoral student at the time, and Timothy Bell, also of Stanford University. They suggested that these events are the consequences of striking a type of lightning to the ground. In the paper, they asserted that following a positively charged lightning strikes to the ground, an electric field is briefly created above the storm. “sudden removal of charge in a lightning discharge leaves a charge imbalance in the medium, which then electromagnetically relaxes and produces luminous glows known as ‘Sprites’ at altitudes 50-70 km, much higher than where lightning occurs”, Inan says.

In the paper that is still one of Inan’s most cited works, they also proposed accelerated atmospheric electrons that are disturbed by striking the lightning to the ground, collide with nitrogen in the upper atmosphere. “Intense impulsive electromagnetic radiation produced by lightning also ionizes Nitrogen molecules as it passes through the ionosphere and produces luminous disks of light known as ‘Elves’ at 100 km altitude”, Inan says.

Ignorosphere

Pasko says recording giant luminous displays above a distant storm by Winckler in 1989 “was totally serendipitous,” but he believes “it became a threshold for a new field of science.” A field that bridged between heavens and also joint forced scientists of two separated branches of physics. The lower electrically neutral atmosphere is the realm of meteorologists, while space physicists deal with charged particles in the upper atmosphere. The region between these two layers is too high for planes and too short for satellites. “Sprites provide windows toward that region, where before discovering of sprites, was best called the “ignorosphere,” Inan says.

“Our understanding of the Earth’s ionosphere, magnetosphere, and radiation belts is important in the context of a better understanding of our planet and its environment,” Inan says. But in terms of real-world applications, sprites and other sources of fluctuations in the ionosphere may interfere with GPS and satellite signals. Also, some scientists speculate that upper-atmospheric lightning might have other effects including on the ozone layer or global warming. Even NASA concerned they might endanger their precious spacecraft during launching and re-entry.

Regardless of these speculative effects, the definitive effect of such electrical phenomena was reviving the scientific curiosity about lightning, 250 years after Franklin historic experiment. Now, in spite of lots of findings thanks to modern pioneers like Inan, we still don’t exactly know how a thundercloud gets the spark needed to initiate a lightning bolt. In fact, years of measurements have shown the electric field in thunderclouds is about ten times smaller than what lightning needs to initiate. Until deciphering this mystery and the physical mechanisms of other astonishing luminous displays through the ethereal world between earth and space, we have no choice other to admit something like the ancient sense of awe and wonder.

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Differentiating Stem Cells into a Scientific Heritage

Hossein Baharvand; an Intimate Profile

A simple but dramatic experiment in 1923, brought German embryologist Hans Spemann (1869-1941), his 1935 Nobel Prize in Physiology or Medicine ‘for his discovery of the organizer effect in embryonic development.’ It is one of some ten such a prize ever went to embryology and one of the rare cases in which a doctoral thesis acknowledged by a Noble Prize.

In the now famous experiment, Spemann and his student and assistant, Hilde Mangold (1898-1924), carried out a transplant in newt embryos. They used two different species of Triturus newts with different colors, so they can be able to distinguish host and donor based on their darkness or lightness. It turned out that a partial conjoined embryo, face to face with its host, could be induced by grafting one special small region of an early newt embryo onto another in the same stage. This small region of the embryo, called Spemann organizer, is responsible for directing the development of a whole embryonic body.

Spemann’s discovery of the effect, now known as embryonic induction, is considered one of the origins of modern developmental biology. The phenomenon of induction, in which one cell, or tissue, directs the development on another one, established beyond question the central importance of cell-cell interactions in embryonic development. Mangold died tragically the next year in a gas explosion in her kitchen when heating milk for her infant son. She never saw her landmark paper was published, and Nobel prizes can’t be awarded posthumously.

Hossein Baharvand, then a high school senior, fell in love with this spectacular episode of history of science, narrated in his twelfth-grade biology textbook. He informed by his teacher that the field which discusses similar subjects is called embryology. Then and there, in the summer of 1989, he decided to become an embryologist. He was a undergraduate biology student at Shiraz University and then accepted for his master of developmental biology at Shahid Beheshti University. He eventually obtained his Ph.D. in Cell and Developmental Biology from Khwarizmi University in 2004.

Work to Make it Work

Hossein Baharvand was born on February 25, 1972, in Isfahan, Iran. “I was a playful and vibrant boy. This attribute to a great extent describes me even today,” he says. “I had many summer jobs like street peddling, masonry, or farming, from elementary to university, and spent my earnings on books and stationeries.” He believes to be influential, one must work hard. He finds satisfaction in working and sees it necessary to refine your soul.

Baharvand was a first child in a crowded family and was expected to help taking care of his siblings. He, nonetheless, somehow saved time to reading books like Persian translations of science fiction by Jules Verne (1828-1905). “There was a book about Albert Schweitzer and his medical aid to African people and difficult times there. It was very inspiring,” he says. He craved to become as effective as people like Schweitzer, as well as Louis Pasteur, Ramón y Cajal, and Marie Curie.

“Your attitude and character are molded in something like an ecological niche. A niche is an n-dimensional hypervolume of which the family is just a part. Another part is social milieu, and still, there are other parts like your wife, friends, society, etc. All of these dimensions add together and join force to make you who you are,” he says.

With such a philosophy, it’s not surprising that he acknowledges many who have incited his interest in developmental biology and helped him flourishing his career. In particular, however, two of them he recalls worth of special noting: The late Dr. Saeid Kazemi Ashtiani (1961-2005), Iranian developmental biologist and director of the Royan Institute; and Dr. Klass Ingo Matthaei, head of the laboratory of gene targeting in John Curtin School of Medical Research, Canberra, Australia, where Baharvand spent five months from February to June 2002 training in production of transgenic and knockout mice.

A Pluripotent Scientist

Returning to Iran, Baharvand started a plan to generate stem cells in the Royan Institute, which was a turning point in Iran’s contribution to translational research and regenerative medicine. He and his team at Royan succeeded to generate, for the first time in Iran, the mouse and human embryonic stem cells and induced pluripotent stem cells, in 2003 and 2008 respectively. He is using this knowledge to make numerous contributions to clinical trials and tissue-specific stem cell transplantation.

Baharvand is a co-author in more than 350 peer-reviewed papers, cited more than 11,000 times so far and led to an h-index of 52. He has edited four books on stem cells – a collection of scientific chapters by different authors - released by international publishers like Springer and Wiley. Baharvand has compiled and translated some books in Persian, mainly about stem cells, and supervised the translation of several guidebooks on scientific career and communication, and also the popular textbook Developmental Biology by Scott F. Gilbert, which is considered the bible of the field.

Baharvand is also on the editorial boards of many journals with high impact factors, like Journal of Biological Chemistry and Scientific Reports. He holds two USA patents and three companies in Iran are operating based on the knowledge he and his team has acquired.

His work has been recognized through the years by many national and international awards and prizes, such as the 2013 Khwarizmi International Award and 2019 TWAS prize in Biology. The later prize, awarded annually by the World Academy of Sciences for the advancement of science in developing countries, granted to Baharvand ‘for his fundamental contribution to the understanding of how pluripotency and differentiation establish and maintain in stem cells.’

The Art of Niche Making

There were many influential figures – Zakariya al-Razi (854-925), Al-Biruni (973-1050), and Avicenna (980-1037), among others - in the history of Iran who made an impressive contribution to human knowledge in medicine. Baharvand hopes that his country would recover its past status in medical science and have its share in ‘tomorrow’s medicine’. He thinks the interdisciplinary field of ‘tomorrow’s medicine’ will include the four components of regenerative medicine, personalized medicine, cancer medicine, and brain and cognitive science. He is trying to set up a prototype of it, as a research hospital, with the help of philanthropists and the government.

Baharvand likes reading Persian classic poetry and employs them in teaching and advising his students. He does hiking, climbing and has trained in the martial art of karate. He spends a lot of time, alone or with his family and friends, in nature. “Nature is our greatest teacher. I consult it a lot to learn. It taught me that evolution is gradual and thus we need to progress steady and continuous too. There is no shortcut in our development, no achievement without hard work, no overnight success. It taught me that if you wish prosperity you should take challenges,” he muses. “Find your own way or even build it from scratch when there is none. The almighty dinosaurs couldn’t cope with the challenges and perished, while the humble mammals found a way out and flourished. For new species to evolve there should be vacant niches. You want new ‘species’? Then create vacant niches and try to expand to fill them.”

The Rejuvenating Elixir

Approaching Immortality through Cell Therapy by Combating One Old Age Chronic Disease at a Time

There was no epoch in the history of humanity but in which man was in frantic search of immortality. Alexander the Great was no exception, and as great as he was and as unbound the world he conquered, it seemed there should not be any reason for him not finding it. He was after something, anything, which spares his life and averts his death.

According to one of the most popular Eastern versions of the story by Nizami Ganjavi (1141–1209), based on the fictional account of ‘Alexander Romance’, an old wise man – probably Khidr – told him about a Fountain of Youth in the Land of Darkness at the edge of the known world – probably modern Abkhazia or the northern Ural – which anyone who drinks from its Water of Life becomes immortal. As the story goes, Alexander under the guidance of Khidr rushed there accompanied by his army. Eventually that fountain Khidr found and drank from it, but it disappeared mysteriously just a moment before Alexander arrived.

Throughout history, many Alexanders have sought ways to restore their youth. One of them, the Russian physician Alexander Bogdanov (1873-1928), surrendered to this wild fantasy of rejuvenation and lost his life to it. In an attempt to become immortal, he committed a series of ill-fated self-experiments in blood transfusion which cost his life because of blood type incompatibility.

Strange as it may seem, there is some truth to Bogdanov thesis and blood may indeed have some rejuvenating properties. In a 2014 study, researchers reported at Nature Medicine that ‘young blood reverses age-related impairments in … mice.’ It turned out that injecting young mice blood plasma to aged mice will help them both in fear responses and spatial learning, thus boosting their ability to learn and think.

For some years after releasing the study results, a San Francisco based clinic called Ambrosia took the opportunity to let its clients enjoy the same effects through injecting the blood of young donors for just 8,000 US dollars! It has now come to a halt, when in February 2019 a warning issued by FDA.

The Onset of Cell Therapy

Injecting organic fluids from another individual as a way to extend human longevity, though became an expensive Silicon Valley tech billionaires’ hobby to cheat death nowadays, has a long history. The eccentric physiologist Charles-Édouard Brown-Séquard (1817-1894) reported in a scientific meeting in Paris in 1890 that he had successfully rejuvenated his “sexual prowess after subcutaneous injection of extracts of monkey testis” at the remarkable age of 72. This scientifically impossible therapy prompted thousands of men trying Brown-Séquard Elixir, as well as launched the field of cell therapy.

Search for immortality, far from being dragged, has accelerated in recent decades both through minor interventions, such as botoxing, lifting, and various supplements, and anti-aging research progressing rapidly in high biotech labs. There is even a whole field of gerontology dedicated to studying the aging process, and big prizes for stopping, delaying, or reversing aging in humans and other mammals with much hype in media. Longevity research has reached a point of maturity now that scientists think they can have a big impact soon with major medical, demographical, sociological, economic, political and environmental consequences.

Solving a Chronic Problem

One practical solution to delay aging is to combat common old age chronic illnesses, such as Parkinson’s and eye diseases. Is it possible to cure these plights of the elderly by injecting some cells to rejuvenate them? This is the expertise of Hossein Baharvand, a developmental biologist of the Royan Institute for Reproductive Biomedicine and Stem Cell, Tehran, Iran, who is a recipient of the 2019 Mustafa  Prize for Parkinson's treatment and eye age-related macular degeneration with cell therapy.

Baharvand tries to promote regenerative medicine using human embryonic stem cells, developmental biology, and biologically inspired engineering. Stem cells, having self-renewal potential (make copies of themselves), are indispensable to cell therapy. They can differentiate into various kinds of cells. Stem cells may be procured from three resources: 1) Embryonic stem cells from embryos prior to implantation; 2) Tissue-specific stem cells or somatic or adult stem cells from bone marrow, skin, blood, and the lining of gut; and 3) Induced pluripotent stem cells (iPS) from reprograming adult cells to retain their undifferentiated properties.

Baharvand and his team at Royan Institute have succeeded to produce rat embryonic stem cells in 2002 and repeated this achievement the next year in human. The decisive moment, however, came about in 2008 when they achieved the technology of producing rat and human iPS in the lab. This made possible founding of different branches of regenerative medicine and producing nervous, heart muscle, liver, and pancreatic beta cells from stem cells in Iran.

This knowledge, for example, led to making dopaminergic progenitor cells from human embryonic stem cells. (A progenitor cell is an undifferentiated cell that, unlike a stem cell, is limited to a set of target cells which it can differentiate to.) Dopamine-releasing neurons which reside the mesencephalon, or midbrain, are the primary source of dopamine – a kind of chemical messenger using in the nervous system of mammals – and their loss may lead to Parkinson's disease.

How We Do It

Parkinson’s disease is a progressive nervous system disorder that affects more than 4 million people worldwide and manifests as the notorious old-age shakiness. The risk of developing this late-onset disease – beginning after age 50 – increases with age, and as the world population is aging, Parkinson’s will become more common, imposing an ever greater economic and societal burden.

Though the human fetal brain has proven as an effective source of dopaminergic progenitor cells for implantation in the midbrain of those suffering from Parkinson’s as early as the second half of the 1980s, fetal stem cells aren’t a reliable source due to their low availability and some ethical consideration. Using human embryonic stem cells as an alternative has shown some promises. But in the long term, there still remain some challenges, such as teratoma - a rare type of tumor containing many tissues - formation and neural overgrowth.

Baharvand and his team in Royan Institute are reporting (in press) a novel strategy of using small molecules to derive midbrain dopaminergic progenitor cells from human embryonic stem cells. They transplanted these progenitors into rats and then a non-human primate model, the rhesus macaque (Macaca mulatta), afflicted by Parkinson’s.

Assessments demonstrate a conspicuous improvement in movements of the monkeys in two years after transplantation without any signs of tumor formation or neural overgrowth in the brain. It seems past failures were due to incomplete specification caused by misdirecting the process of differentiation. Now they are thinking of translating this cell therapy achievement to the human condition.

This is similar to what they did in 2012 to cure age-related macular degeneration, which led to blurred vision and, if remains untreated, blindness in the elderly. This condition is a result of damage to the macula area of the eye retina which is a layer of pigmented cells and plays an essential role in visual function.

Baharvand and his team at Royan Institute proposed, in a couple of papers in the prestigious journal of Stem Cells and Development in 2012, a method for directing the differentiation of human induced pluripotent stem cells to the retinal pigmented epithelium. These findings, first in rabbits and then in humans, provided an unprecedentedly simple and effective tool for cell replacement therapies in retinal diseases.

Plan B

It seems that cell therapy is becoming our most effective weapon in fighting against chronic diseases that are at the top of the list in old age. It is not equal to achieve eternal life, literally, but it can extend, as researchers reasonably expect, the lifespan of humankind as the best next option, and double the biblical quota of three scores and ten. And it is a healthy functional extension too. Wouldn’t you dream of bearing no pain when you are gained already? To have enough time to accomplish to your fulfillment any lengthy project which cannot be completed in a currently short human life? Well, this is Plan B: Securing an extended adult life so we can invest more in each individual, instead of rapid generation turnover.

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In the Right Place at the Right Time

Mohammad Abdolahad; an Intimate Profile

A modern airliner has about 10 thousand sensors constantly recording information that informs pilots about the plane’s performance. But more importantly, the huge amount of data makes it possible to forecast mechanical problems that be easily corrected if the plane is not high in the sky. The system has an extraordinary performance: aviation accidents are extremely rare, with the chance of a passenger being killed on a flight at about eight million-to-one.

Our bodies are equipped with analogous information systems that could alert about any forthcoming disease. However, reading this critical information needs to have comprehensive access to the human body at the cellular or molecular levels, which unfortunately we haven’t. But what about a certain disease, the deadliest one: cancer. This is the idea that S. Mohajerzade, professor of electrical engineering at the University of Tehran, talked about with Mohammad Abdolahad when he was a Ph.D. student.

A Nice Short Chat

Abdolahad, now an associate professor of electrical engineering also at the University of Tehran, recalls “One day, he happened to talk to me about a professor who has come from the US and says a lot of interesting things about cancerous cells.” At the time, as a newcomer Ph.D. student in electrical engineering, he had nothing to do with cancer and was planning to do his thesis in the field of photonic. But that short chat with Mohajerzadeh dramatically changed his mind later.

Soon after early studies, Abdolahad found the biological science of cancer with the translation of electronics as a really amazing and interesting field of research. When he decided to start his thesis in the field under the supervision of Mohajerzadeh, it turned out that he was going to have a hard time making any progress, without a strong background in biological science. Therefore, in addition to his routine studies in electrical engineering, he began to study medical science, particularly about cancer, pathology, cell’s biochemical behavior and also its translation into electronics. “Mohajerzadeh prepared all the initial facilities and even asked one of the professors in biology (M. Habibi Rezaei) to teach us biotechnology,” Abdolahad says.

During the period that took two years, he published some papers and invented devices in the field of the electrical behavior of cancerous and healthy cells which some of them were unprecedented. After receiving Ph.D., because of these remarkable achievements, the University of Tehran gave Abdolahad a great opportunity to follow his research in an allocated lab. In the meantime, the Council of Microelectronic Technology of Vice-Presidency of Science and Technology supported him through a research fund.

Under Abdolahad coordination, a group of experts of different disciplines gathered at Nano-Bio Electronic Devices Lab, in order to research on diagnostic systems, methods, and tools for cancer. “When our research got to start, depends on our needs, we should use various expertise,” he says. Coming years was a period of progress and achievement for Abdolahad and his research group, including the development of a new microelectronic biochip, called Metas-Chip that can precisely identify the presence of micro-metastasis in biopsy samples.

One of the key influences on his career was his continuous connections with hospitals and biological research centers. “Thanks to my colleagues at Tehran University of Medical Sciences and MAHAK hospital, when the development process of Metas-Chip was done, we had the chance to investigate the device’s performance under clinical trials,” he says.

Publishing the paper about Metas-Cip in Nature Communications was a 10 months challenge that after many go and forth between referees and research groups, came to an end in December 2017. But for Abdolahad, it was not the end of the story. “By publishing the paper, we introduced the technology but producing a well-designed and user-friendly product was another major step,” he says. So he took the step, and in coalition with a group of industrial designers turned the device to an integrated final product.

Great Expectations

Abdolahad was born in Tehran, Iran, in 1982. During recent years, he achieved much success including filing more than 20 US patents and publishing more than 50 papers in prominent journals, mostly in the field of cancer detection by nanoelectronic devices. He won the “Best Young Inventor” medal of WIPO in 2016 based on his research and developed systems on the technology of cancer diagnosis. He received the “Best Young Scientist from Iran Academy of Science”. Since 2016, he is an adjunct professor at Tehran University of Medical Sciences. He is undergoing to develop the “electrotechnical oncosurgery” as a new joint Fellowship-Postdoc between surgery and electrical engineering disciplines.

Abdolahad describes his field of research as “fighting cancer with the assist of electronics in terms of diagnostics, from science to product.” In fact, he is working at the intersection of diverse scientific disciplines, a key point where breakthroughs in science often happen. At age 37, it seems he is in the right place at the right time. He is thinking about another ambitious goal, but he says “let me not to say. It is confidential.” However, he believes “finding the electrical signature of cancer initiation”, and “how to electrically control the cancer function to prevent its destructive effects on the body” are two of the most important questions in his field of research that their answers may lead to breakthroughs.

He describes himself as “a person with plenty of questions, someone whose knowledge is always lower than what is needed to tackle his unsolved problems but wants to know more and more”. He believes, he may be able to help humans for a better life, if he reduces his ignorance and increases his experience. “I believe in an honest life in which you want to help human beings, regardless of their religion or race. I want to be a real Muslim.” Out of his lab, when he is not doing research, he prefers to spend time with his family and play with his babies.

When it’s not too late

Recent developments in cancer diagnosis biosensors brought the technology on the verge of commercialization

Sometimes you would know the smell of your close relatives, even blindfolded. This is not about the smells of their perfumes or the detergents they use for laundry. You can vividly just recognize the smells of themselves. The odor of our bodies is made of thousands of organic compounds. Just like the fingerprint, the complex mixture of molecules in the odor-print is unique and could reveal a lot of things about us, including age, genetics, lifestyle, maybe hometown or job, or even our physical health status and its underlying metabolic processes.

This is not a secret revealed by modern science. In the traditional medicine of ancient Greek and Chinese, using a patient’s scent was a common way to make diagnoses. Even modern medical research confirms that the smell of skin, breath or bodily fluids can suggest if someone is ill. For example, the exhale of diabetic patients sometimes smells like rotten apples. Using olfaction as a noninvasive mean of diagnosis seems to be a very interesting idea, but not every physician has a good sense of smell and their nose couldn’t be a reliable precise tool. However, in a more realistic scenario, our bodies are full of biomarkers which can provide critical data about our health status, if we have the right tools for reading some of them. This is why researchers have been trying for decades to build biosensors that could diagnose illness in a quick, cheap, noninvasive and reliable way.

Alliance

The history of biosensors dates back to more than a century ago, when Max Cremer, a German physiologist (1865-1935), invented the glass electrode in 1906. After the introduction of the concept of pH (hydrogen ion concentration) in 1909 and an electrode for pH measurements in 1922, researchers tried to demonstrate the capabilities of the early form of biosensors. However, it was only in 1956 that the first true biosensor was developed by Leland C.Clark, American biochemist (1918-2005). He is known as the “father of biosensor” and his invention of an electrode for the detection of glucose eventually led to the development of the first commercial biosensors in 1975.

Since then, the field of biosensors has experienced remarkable progress and the field is now a multidisciplinary area of research that any achievement in it needs a coalition of scientists who know how to bridge the foundations of basic sciences with electronics, micro-electro-mechanics, nanotechnology, and medicine. In recent years, such a group of elite researchers is gathered in Nano-Bio Electronic Devices Lab at the University of Tehran. Within the short time of starting this initiative, Mohammad Abdolahad, coordinator of the lab and associate professor of electrical and computer engineering department, and his colleagues introduced several new miniaturized diagnostic systems. Abdolahad, one of the laureates of the 2019 Mustafa Prize from Islamic countries, and his team achieved much success, including filing more than 20 US patents and publishing more than 50 papers in prominent journals. In a 2017 paper published in Nature Communications, Abdolahad introduced a new microelectronic biochip, called Metas-Chip that can precisely identify the presence of micro-metastasis in biopsy samples.

One of the biggest promises of biosensors is that they can diagnose diseases when conventional tests cannot. And, when it comes to early diagnosis, there is no more critical disease than cancer. Therefore much of research in the field of the biosensor is aimed to find new methods and design new devices for cancer diagnosis. Identifying metastatic cancer cells in a sample resected from the secondary tissue of the patients by pathological methods is the most important step in cancer staging and therapeutic regimes.

But these methods are designed to track the presence of abnormally aggressive cells in the samples that are prepared from removed tissues by certain procedures. This means with these pathological methods, there is always a chance to miss the target. “Although cancer cells are detectable in some cases, they might be rare or only exist in regions of the removed sample that are not investigated by the pathologist, and preventing missing any aggressive cancer cells is time-consuming and expensive,” Abdolahad says.

Golden rule

It is said that cancer is not just one disease. In fact, there are more than 200 types of cancer and all of them caused by the uncontrollable growth of cells in the body. Deaths from cancer usually caused by secondary tumors which are the consequence of cancer cell proliferation to other parts of the body in a process known as metastasis. “Metastasis happens when cancer cells acquire a migratory to invasive phenotype, initiated from groupings of cells that appear to break off from primary tumors,” Abdolahad says.

In spite of much progress in understanding the nature of cancer, the devastating effects of it on patients has remained almost unchanged for many years. In fact, the overall death rates of all types of cancers in the 2000s were about the same as in the 1950s. On the other hand, the golden rule in the fight against cancer is also still the same: half of the battle is won based on early detection. However, detecting the early stages of cancer, long before physical symptoms occur, can be very difficult. The approach that Abdolahad introduced in the paper, makes it possible to capture the metastatic cells with a simple, fast, and chemistry-free method in small biopsy samples, which will improve the diagnostic impact of existing pathological methods before surgery or treatments.

Biosensor technology is an evolving field and more efficient, sensitive and reliable devices are being developed all the time. Yet very few of them make it to clinical trials for cancer diagnosis. However, the cooperation between Abdolahad’s research group and Tehran University of Medical Sciences made it possible to investigate Metas-Chip under clinical trials. And, the device, filed US patent, demonstrated its remarkable capabilities. “Metas-Chip identified the metastasis in more than 70 breast cancer patients, in less than 5 hours. Moreover, it detected the metastasis in lymph nodes of nine patients who were missed by conventional pathological procedures,” Abdolahad says. In the following, further tests on the missed samples confirmed the validity of the chip’s diagnosis.

High levels of investment into translational research worldwide in recent years, especially, for healthcare applications, paved the way for biosensor technologies to develop faster. This can lead to a coalition between industry and academia to provide commercially viable products. Achieving the goal needs engineering and physical scientists that have a better understanding of biology, and biochemists and biologists that have a greater awareness of the capabilities of various technologies. The alliance of experts of different disciplines, like one formed by the efforts of Abdolahad and his colleagues at the University of Tehran, is a very promising situation that will lead to the commercialization of advanced and novel products.