Designation: Professor of Stem Cells and Developmental Biology
at Royan institute, Iran
Work: Parkinson's treatment and Eye AMD with Stem Cell
Field of the Prize: Stem Cell Biology
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.
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.