Tag Archives: Nobel Prize in Physiology or Medicine

2023 Nobel prizes (medicine, physics, and chemistry)

Medicine

Two people (Katalin Karikó and Drew Weissman) were awarded the prize in medicine according to the October 2, 2023 Nobel Prize press release, Note: Links have been removed,

The Nobel Assembly at Karolinska Institutet [Sweden]
has today decided to award
the 2023 Nobel Prize in Physiology or Medicine
jointly to
Katalin Karikó and Drew Weissman
for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19
The discoveries by the two Nobel Laureates were critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020. Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.
Vaccines before the pandemic
Vaccination stimulates the formation of an immune response to a particular pathogen. This gives the body a head start in the fight against disease in the event of a later exposure. Vaccines based on killed or weakened viruses have long been available, exemplified by the vaccines against polio, measles, and yellow fever. In 1951, Max Theiler was awarded the Nobel Prize in Physiology or Medicine for developing the yellow fever vaccine.
Thanks to the progress in molecular biology in recent decades, vaccines based on individual viral components, rather than whole viruses, have been developed. Parts of the viral genetic code, usually encoding proteins found on the virus surface, are used to make proteins that stimulate the formation of virus-blocking antibodies. Examples are the vaccines against the hepatitis B virus and human papillomavirus. Alternatively, parts of the viral genetic code can be moved to a harmless carrier virus, a “vector.” This method is used in vaccines against the Ebola virus. When vector vaccines are injected, the selected viral protein is produced in our cells, stimulating an immune response against the targeted virus.
Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics. Therefore, researchers have long attempted to develop vaccine technologies independent of cell culture, but this proved challenging.

Illustration of methods for vaccine production before the COVID-19 pandemic. — *Figure 1.* Methods for vaccine production before the COVID-19 pandemic. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén

mRNA vaccines: A promising idea
In our cells, genetic information encoded in DNA is transferred to messenger RNA (mRNA), which is used as a template for protein production. During the 1980s, efficient methods for producing mRNA without cell culture were introduced, called in vitro transcription. This decisive step accelerated the development of molecular biology applications in several fields. Ideas of using mRNA technologies for vaccine and therapeutic purposes also took off, but roadblocks lay ahead. In vitro transcribed mRNA was considered unstable and challenging to deliver, requiring the development of sophisticated carrier lipid systems to encapsulate the mRNA. Moreover, in vitro-produced mRNA gave rise to inflammatory reactions. Enthusiasm for developing the mRNA technology for clinical purposes was, therefore, initially limited.
These obstacles did not discourage the Hungarian biochemist Katalin Karikó, who was devoted to developing methods to use mRNA for therapy. During the early 1990s, when she was an assistant professor at the University of Pennsylvania, she remained true to her vision of realizing mRNA as a therapeutic despite encountering difficulties in convincing research funders of the significance of her project. A new colleague of Karikó at her university was the immunologist Drew Weissman. He was interested in dendritic cells, which have important functions in immune surveillance and the activation of vaccine-induced immune responses. Spurred by new ideas, a fruitful collaboration between the two soon began, focusing on how different RNA types interact with the immune system.
The breakthrough
Karikó and Weissman noticed that dendritic cells recognize in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules. They wondered why the in vitro transcribed mRNA was recognized as foreign while mRNA from mammalian cells did not give rise to the same reaction. Karikó and Weissman realized that some critical properties must distinguish the different types of mRNA.
RNA contains four bases, abbreviated A, U, G, and C, corresponding to A, T, G, and C in DNA, the letters of the genetic code. Karikó and Weissman knew that bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not. They wondered if the absence of altered bases in the in vitro transcribed RNA could explain the unwanted inflammatory reaction. To investigate this, they produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells. The results were striking: The inflammatory response was almost abolished when base modifications were included in the mRNA. This was a paradigm change in our understanding of how cells recognize and respond to different forms of mRNA. Karikó and Weissman immediately understood that their discovery had profound significance for using mRNA as therapy. These seminal results were published in 2005, fifteen years before the COVID-19 pandemic.

Illustration of the four different bases mRNA contains. — *Figure 2.* mRNA contains four different bases, abbreviated A, U, G, and C. The Nobel Laureates discovered that base-modified mRNA can be used to block activation of inflammatory reactions (secretion of signaling molecules) and increase protein production when mRNA is delivered to cells. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén

In further studies published in 2008 and 2010, Karikó and Weissman showed that the delivery of mRNA generated with base modifications markedly increased protein production compared to unmodified mRNA. The effect was due to the reduced activation of an enzyme that regulates protein production. Through their discoveries that base modifications both reduced inflammatory responses and increased protein production, Karikó and Weissman had eliminated critical obstacles on the way to clinical applications of mRNA.
mRNA vaccines realized their potential
Interest in mRNA technology began to pick up, and in 2010, several companies were working on developing the method. Vaccines against Zika virus and MERS-CoV were pursued; the latter is closely related to SARS-CoV-2. After the outbreak of the COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed. Protective effects of around 95% were reported, and both vaccines were approved as early as December 2020.
The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccines against other infectious diseases. In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types.
Several other vaccines against SARS-CoV-2, based on different methodologies, were also rapidly introduced, and together, more than 13 billion COVID-19 vaccine doses have been given globally. The vaccines have saved millions of lives and prevented severe disease in many more, allowing societies to open and return to normal conditions. Through their fundamental discoveries of the importance of base modifications in mRNA, this year’s Nobel laureates critically contributed to this transformative development during one of the biggest health crises of our time.
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Read more about this year’s prize
Scientific background: Discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19
Katalin Karikó was born in 1955 in Szolnok, Hungary. She received her PhD from Szeged’s University in 1982 and performed postdoctoral research at the Hungarian Academy of Sciences in Szeged until 1985. She then conducted postdoctoral research at Temple University, Philadelphia, and the University of Health Science, Bethesda. In 1989, she was appointed Assistant Professor at the University of Pennsylvania, where she remained until 2013. After that, she became vice president and later senior vice president at BioNTech RNA Pharmaceuticals. Since 2021, she has been a Professor at Szeged University and an Adjunct Professor at Perelman School of Medicine at the University of Pennsylvania.
Drew Weissman was born in 1959 in Lexington, Massachusetts, USA. He received his MD, PhD degrees from Boston University in 1987. He did his clinical training at Beth Israel Deaconess Medical Center at Harvard Medical School and postdoctoral research at the National Institutes of Health. In 1997, Weissman established his research group at the Perelman School of Medicine at the University of Pennsylvania. He is the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovations.

The University of Pennsylvania October 2, 2023 news release is a very interesting announcement (more about why it’s interesting afterwards), Note: Links have been removed,

The University of Pennsylvania messenger RNA pioneers whose years of scientific partnership unlocked understanding of how to modify mRNA to make it an effective therapeutic—enabling a platform used to rapidly develop lifesaving vaccines amid the global COVID-19 pandemic—have been named winners of the 2023 Nobel Prize in Physiology or Medicine. They become the 28^th and 29^th Nobel laureates affiliated with Penn, and join nine previous Nobel laureates with ties to the University of Pennsylvania who have won the Nobel Prize in Medicine.
Nearly three years after the rollout of mRNA vaccines across the world, Katalin Karikó, PhD, an adjunct professor of Neurosurgery in Penn’s Perelman School of Medicine, and Drew Weissman, MD, PhD, the Roberts Family Professor of Vaccine Research in the Perelman School of Medicine, are recipients of the prize announced this morning by the Nobel Assembly in Solna, Sweden.
After a chance meeting in the late 1990s while photocopying research papers, Karikó and Weissman began investigating mRNA as a potential therapeutic. In 2005, they published a key discovery: mRNA could be altered and delivered effectively into the body to activate the body’s protective immune system. The mRNA-based vaccines elicited a robust immune response, including high levels of antibodies that attack a specific infectious disease that has not previously been encountered. Unlike other vaccines, a live or attenuated virus is not injected or required at any point.
When the COVID-19 pandemic struck, the true value of the pair’s lab work was revealed in the most timely of ways, as companies worked to quickly develop and deploy vaccines to protect people from the virus. Both Pfizer/BioNTech and Moderna utilized Karikó and Weissman’s technology to build their highly effective vaccines to protect against severe illness and death from the virus. In the United States alone, mRNA vaccines make up more than 655 million total doses of SARS-CoV-2 vaccines that have been administered since they became available in December 2020.
…
Editor’s Note: The Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines both use licensed University of Pennsylvania technology. As a result of these licensing relationships, Penn, Karikó and Weissman have received and may continue to receive significant financial benefits in the future based on the sale of these products. BioNTech provides funding for Weissman’s research into the development of additional infectious disease vaccines.

Science can be brutal

Now for the interesting bit: it’s in my March 5, 2021 posting (mRNA, COVID-19 vaccines, treating genetic diseases before birth, and the scientist who started it all),

…
Before messenger RNA was a multibillion-dollar idea, it was a scientific backwater. And for the Hungarian-born scientist behind a key mRNA discovery, it was a career dead-end.
Katalin Karikó spent the 1990s collecting rejections. Her work, attempting to harness the power of mRNA to fight disease, was too far-fetched for government grants, corporate funding, and even support from her own colleagues.
…
“Every night I was working: grant, grant, grant,” Karikó remembered, referring to her efforts to obtain funding. “And it came back always no, no, no.”
By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted. [emphasis mine] She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.
She was back to the lower rungs of the scientific academy.
“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Karikó said.
There’s no opportune time for demotion, but 1995 had already been uncommonly difficult. Karikó had recently endured a cancer scare, and her husband was stuck in Hungary sorting out a visa issue. Now the work to which she’d devoted countless hours was slipping through her fingers.
…
In time, those better experiments came together. After a decade of trial and error, Karikó and her longtime collaborator at Penn — Drew Weissman [emphasis mine], an immunologist with a medical degree and Ph.D. from Boston University — discovered a remedy for mRNA’s Achilles’ heel.
…

You can get the whole story from my March 5, 2021 posting, scroll down to the “mRNA—it’s in the details, plus, the loneliness of pioneer researchers, a demotion, and squabbles” subhead. If you are very curious about mRNA and the rough and tumble of the world of science, there’s my August 20, 2021 posting “Getting erased from the mRNA/COVID-19 story” where Ian MacLachlan is featured as a researcher who got erased and where Karikó credits his work.

‘Rowing Mom Wins Nobel’ (credit: rowing website Row 2K)

Karikó’s daughter is a two-time gold medal Olympic athlete as the Canadian Broadcasting Corporation’s (CBC) radio programme, As It Happens, notes in an interview with the daughter (Susan Francia). From an October 4, 2023 As It Happens article (with embedded audio programme excerpt) by Sheena Goodyear,

Olympic gold medallist Susan Francia is coming to terms with the fact that she’s no longer the most famous person in her family.
That’s because the retired U.S. rower’s mother, Katalin Karikó, just won a Nobel Prize in Medicine. The biochemist was awarded alongside her colleague, vaccine researcher Drew Weissman, for their groundbreaking work that led to the development of COVID-19 vaccines.
“Now I’m like, ‘Shoot! All right, I’ve got to work harder,'” Francia said with a laugh during an interview with As It Happens host Nil Köksal.
But in all seriousness, Francia says she’s immensely proud of her mother’s accomplishments. In fact, it was Karikó’s fierce dedication to science that inspired Francia to win Olympic gold medals in 2008 and 2012.
“Sport is a lot like science in that, you know, you have a passion for something and you just go and you train, attain your goal, whether it be making this discovery that you truly believe in, or for me, it was trying to be the best in the world,” Francia said.
“It’s a grind and, honestly, I love that grind. And my mother did too.”
…
… one of her [Karikó] favourite headlines so far comes from a little blurb on the rowing website Row 2K: “Rowing Mom Wins Nobel.”
…
Nowadays, scientists are trying to harness the power of mRNA to fight cancer, malaria, influenza and rabies. But when Karikó first began her work, it was a fringe concept. For decades, she toiled in relative obscurity, struggling to secure funding for her research.
“That’s also that same passion that I took into my rowing,” Francia said.
But even as Karikó struggled to make a name for herself, she says her own mother, Zsuzsanna, always believed she would earn a Nobel Prize one day.
Every year, as the Nobel Prize announcement approached, she would tell Karikó she’d be watching for her name.
“I was laughing [and saying] that, ‘Mom, I am not getting anything,'” she said.
But her mother, who died a few years ago, ultimately proved correct.
…

Congratulations to both Katalin Karikó and Drew Weissman and thank you both for persisting!

Physics

This prize is for physics at the attoscale.

Aaron W. Harrison (Assistant Professor of Chemistry, Austin College, Texas, US) attempts an explanation of an attosecond in his October 3, 2023 essay (in English “What is an attosecond? A physical chemist explains the tiny time scale behind Nobel Prize-winning research” and in French “Nobel de physique : qu’est-ce qu’une attoseconde?”) for The Conversation, Note: Links have been removed,

…
“Atto” is the scientific notation prefix that represents 10^-18, which is a decimal point followed by 17 zeroes and a 1. So a flash of light lasting an attosecond, or 0.000000000000000001 of a second, is an extremely short pulse of light.
In fact, there are approximately as many attoseconds in one second as there are seconds in the age of the universe.
Previously, scientists could study the motion of heavier and slower-moving atomic nuclei with femtosecond (10^-15) light pulses. One thousand attoseconds are in 1 femtosecond. But researchers couldn’t see movement on the electron scale until they could generate attosecond light pulses – electrons move too fast for scientists to parse exactly what they are up to at the femtosecond level.
…

Harrison does a very good job of explaining something that requires a leap of imagination. He also explains why scientists engage in attosecond research. h/t October 4, 2023 news item on phys.org

Amelle Zaïr (Imperial College London) offers a more technical explanation in her October 4, 2023 essay about the 2023 prize winners for The Conversation. h/t October 4, 2023 news item on phys.org

Main event

Here’s the October 3, 2023 Nobel Prize press release, Note: A link has been removed,

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics 2023 to
Pierre Agostini
The Ohio State University, Columbus, USA
Ferenc Krausz
Max Planck Institute of Quantum Optics, Garching and Ludwig-Maximilians-Universität München, Germany
Anne L’Huillier
Lund University, Sweden
“for experimental methods that generate attosecond pulses of light for the study of electron dynamics in matter”
Experiments with light capture the shortest of moments
The three Nobel Laureates in Physics 2023 are being recognised for their experiments, which have given humanity new tools for exploring the world of electrons inside atoms and molecules. Pierre Agostini, Ferenc Krausz and Anne L’Huillier have demonstrated a way to create extremely short pulses of light that can be used to measure the rapid processes in which electrons move or change energy.
Fast-moving events flow into each other when perceived by humans, just like a film that consists of still images is perceived as continual movement. If we want to investigate really brief events, we need special technology. In the world of electrons, changes occur in a few tenths of an attosecond – an attosecond is so short that there are as many in one second as there have been seconds since the birth of the universe.
The laureates’ experiments have produced pulses of light so short that they are measured in attoseconds, thus demonstrating that these pulses can be used to provide images of processes inside atoms and molecules.
In 1987, Anne L’Huillier discovered that many different overtones of light arose when she transmitted infrared laser light through a noble gas. Each overtone is a light wave with a given number of cycles for each cycle in the laser light. They are caused by the laser light interacting with atoms in the gas; it gives some electrons extra energy that is then emitted as light. Anne L’Huillier has continued to explore this phenomenon, laying the ground for subsequent breakthroughs.
In 2001, Pierre Agostini succeeded in producing and investigating a series of consecutive light pulses, in which each pulse lasted just 250 attoseconds. At the same time, Ferenc Krausz was working with another type of experiment, one that made it possible to isolate a single light pulse that lasted 650 attoseconds.
The laureates’ contributions have enabled the investigation of processes that are so rapid they were previously impossible to follow.
“We can now open the door to the world of electrons. Attosecond physics gives us the opportunity to understand mechanisms that are governed by electrons. The next step will be utilising them,” says Eva Olsson, Chair of the Nobel Committee for Physics.
There are potential applications in many different areas. In electronics, for example, it is important to understand and control how electrons behave in a material. Attosecond pulses can also be used to identify different molecules, such as in medical diagnostics.
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Read more about this year’s prize
Popular science background: Electrons in pulses of light (pdf)
Scientific background: “For experimental methods that generate attosecond pulses of light for the study of electron dynamics in matter” (pdf)
Pierre Agostini. PhD 1968 from Aix-Marseille University, France. Professor at The Ohio State University, Columbus, USA.
Ferenc Krausz, born 1962 in Mór, Hungary. PhD 1991 from Vienna University of Technology, Austria. Director at Max Planck Institute of Quantum Optics, Garching and Professor at Ludwig-Maximilians-Universität München, Germany.
Anne L’Huillier, born 1958 in Paris, France. PhD 1986 from University Pierre and Marie Curie, Paris, France. Professor at Lund University, Sweden.

A Canadian connection?

An October 3, 2023 CBC online news item from the Associated Press reveals a Canadian connection of sorts ,

Three scientists have won the Nobel Prize in physics Tuesday for giving us the first split-second glimpse into the superfast world of spinning electrons, a field that could one day lead to better electronics or disease diagnoses.
The award went to French-Swedish physicist Anne L’Huillier, French scientist Pierre Agostini and Hungarian-born Ferenc Krausz for their work with the tiny part of each atom that races around the centre, and that is fundamental to virtually everything: chemistry, physics, our bodies and our gadgets.
Electrons move around so fast that they have been out of reach of human efforts to isolate them. But by looking at the tiniest fraction of a second possible, scientists now have a “blurry” glimpse of them, and that opens up whole new sciences, experts said.
“The electrons are very fast, and the electrons are really the workforce in everywhere,” Nobel Committee member Mats Larsson said. “Once you can control and understand electrons, you have taken a very big step forward.”
L’Huillier is the fifth woman to receive a Nobel in Physics.
…
L’Huillier was teaching basic engineering physics to about 100 undergraduates at Lund when she got the call that she had won, but her phone was on silent and she didn’t pick up. She checked it during a break and called the Nobel Committee.
Then she went back to teaching.
…
Agostini, an emeritus professor at Ohio State University, was in Paris and could not be reached by the Nobel Committee before it announced his win to the world
…

Here’s the Canadian connection (from the October 3, 2023 CBC online news item),

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Krausz, of the Max Planck Institute of Quantum Optics and Ludwig Maximilian University of Munich, told reporters that he was bewildered.
“I have been trying to figure out since 11 a.m. whether I’m in reality or it’s just a long dream,” the 61-year-old said.
Last year, Krausz and L’Huillier won the prestigious Wolf prize in physics for their work, sharing it with University of Ottawa scientist Paul Corkum [emphasis mine]. Nobel prizes are limited to only three winners and Krausz said it was a shame that it could not include Corkum.
Corkum was key to how the split-second laser flashes could be measured [emphasis mine], which was crucial, Krausz said.
…

Congratulations to Pierre Agostini, Ferenc Krausz and Anne L’Huillier and a bow to Paul Corkum!

For those who are curious. a ‘Paul Corkum’ search should bring up a few postings on this blog but I missed this piece of news, a May 4, 2023 University of Ottawa news release about Corkum and the 2022 Wolf Prize, which he shared with Krausz and L’Huillier,

Chemistry

There was a little drama where this prize was concerned, It was announced too early according to an October 4, 2023 news item on phys.org and, again, in another October 4, 2023 news item on phys.org (from the Oct. 4, 2023 news item by Karl Ritter for the Associated Press),

Oops! Nobel chemistry winners are announced early in a rare slip-up
The most prestigious and secretive prize in science ran headfirst into the digital era Wednesday when Swedish media got an emailed press release revealing the winners of the Nobel Prize in chemistry and the news prematurely went public.
…

Here’s the fully sanctioned October 4 , 2023 Nobel Prize press release, Note: A link has been removed,

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2023 to
Moungi G. Bawendi
Massachusetts Institute of Technology (MIT), Cambridge, MA, USA
Louis E. Brus
Columbia University, New York, NY, USA
Alexei I. Ekimov
Nanocrystals Technology Inc., New York, NY, USA
“for the discovery and synthesis of quantum dots”
They planted an important seed for nanotechnology
The Nobel Prize in Chemistry 2023 rewards the discovery and development of quantum dots, nanoparticles so tiny that their size determines their properties. These smallest components of nanotechnology now spread their light from televisions and LED lamps, and can also guide surgeons when they remove tumour tissue, among many other things.
Everyone who studies chemistry learns that an element’s properties are governed by how many electrons it has. However, when matter shrinks to nano-dimensions quantum phenomena arise; these are governed by the size of the matter. The Nobel Laureates in Chemistry 2023 have succeeded in producing particles so small that their properties are determined by quantum phenomena. The particles, which are called quantum dots, are now of great importance in nanotechnology.
“Quantum dots have many fascinating and unusual properties. Importantly, they have different colours depending on their size,” says Johan Åqvist, Chair of the Nobel Committee for Chemistry.
Physicists had long known that in theory size-dependent quantum effects could arise in nanoparticles, but at that time it was almost impossible to sculpt in nanodimensions. Therefore, few people believed that this knowledge would be put to practical use.
However, in the early 1980s, Alexei Ekimov succeeded in creating size-dependent quantum effects in coloured glass. The colour came from nanoparticles of copper chloride and Ekimov demonstrated that the particle size affected the colour of the glass via quantum effects.
A few years later, Louis Brus was the first scientist in the world to prove size-dependent quantum effects in particles floating freely in a fluid.
In 1993, Moungi Bawendi revolutionised the chemical production of quantum dots, resulting in almost perfect particles. This high quality was necessary for them to be utilised in applications.
Quantum dots now illuminate computer monitors and television screens based on QLED technology. They also add nuance to the light of some LED lamps, and biochemists and doctors use them to map biological tissue.
Quantum dots are thus bringing the greatest benefit to humankind. Researchers believe that in the future they could contribute to flexible electronics, tiny sensors, thinner solar cells and encrypted quantum communication – so we have just started exploring the potential of these tiny particles.
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Read more about this year’s prize
Popular science background: They added colour to nanotechnology (pdf)
Scientific background: Quantum dots – seeds of nanoscience (pdf)
Moungi G. Bawendi, born 1961 in Paris, France. PhD 1988 from University of Chicago, IL, USA. Professor at Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Louis E. Brus, born 1943 in Cleveland, OH, USA. PhD 1969 from Columbia University, New York, NY, USA. Professor at Columbia University, New York, NY, USA.
Alexei I. Ekimov, born 1945 in the former USSR. PhD 1974 from Ioffe Physical-Technical Institute, Saint Petersburg, Russia. Formerly Chief Scientist at Nanocrystals Technology Inc., New York, NY, USA.

The most recent ‘quantum dot’ (a particular type of nanoparticle) story here is a January 5, 2023 posting, “Can I have a beer with those carbon quantum dots?“

Proving yet again that scientists can have a bumpy trip to a Nobel prize, an October 4, 2023 news item on phys.org describes how one of the winners flunked his first undergraduate chemistry test, Note: Links have been removed,

Talk about bouncing back. MIT professor Moungi Bawendi is a co-winner of this year’s Nobel chemistry prize for helping develop “quantum dots”—nanoparticles that are now found in next generation TV screens and help illuminate tumors within the body.
But as an undergraduate, he flunked his very first chemistry exam, recalling that the experience nearly “destroyed” him.
The 62-year-old of Tunisian and French heritage excelled at science throughout high school, without ever having to break a sweat.
But when he arrived at Harvard University as an undergraduate in the late 1970s, he was in for a rude awakening.
…

You can find more about the winners and quantum dots in an October 4, 2023 news item on Nanowerk and in Dr. Andrew Maynard’s (Professor of Advanced Technology Transitions, Arizona State University) October 4, 2023 essay for The Conversation (h/t October 4, 2023 news item on phys.org), Note: Links have been removed,

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This year’s prize recognizes Moungi Bawendi, Louis Brus and Alexei Ekimov for the discovery and development of quantum dots. For many years, these precisely constructed nanometer-sized particles – just a few hundred thousandths the width of a human hair in diameter – were the darlings of nanotechnology pitches and presentations. As a researcher and adviser on nanotechnology [emphasis mine], I’ve [Dr. Andrew Maynard] even used them myself when talking with developers, policymakers, advocacy groups and others about the promise and perils of the technology.
The origins of nanotechnology predate Bawendi, Brus and Ekimov’s work on quantum dots – the physicist Richard Feynman speculated on what could be possible through nanoscale engineering as early as 1959, and engineers like Erik Drexler were speculating about the possibilities of atomically precise manufacturing in the the 1980s. However, this year’s trio of Nobel laureates were part of the earliest wave of modern nanotechnology where researchers began putting breakthroughs in material science to practical use.
Quantum dots brilliantly fluoresce: They absorb one color of light and reemit it nearly instantaneously as another color. A vial of quantum dots, when illuminated with broad spectrum light, shines with a single vivid color. What makes them special, though, is that their color is determined by how large or small they are. Make them small and you get an intense blue. Make them larger, though still nanoscale, and the color shifts to red.
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The wavelength of light a quantum dot emits depends on its size. Maysinger, Ji, Hutter, Cooper, CC BY

There’s also an October 4, 2023 overview article by Tekla S. Perry and Margo Anderson for the IEEE Spectrum about the magazine’s almost twenty-five years of reporting on quantum dots

Red blue and green dots mass in rows, with some dots moving away

Image credit: Brandon Palacio/IEEE Spectrum

Your Guide to the Newest Nobel Prize: Quantum Dots
What you need to know—and what we’ve reported—about this year’s Chemistry award
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It’s not a long article and it has a heavy focus on the IEEEE’s (Institute of Electrical and Electtronics Engineers) the road quantum dots have taken to become applications and being commercialized.

Congratulations to Moungi Bawendi, Louis Brus, and Alexei Ekimov!

Macchiarini controversy and synthetic trachea transplants (part 2 of 2)

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For some bizarre frosting on this disturbing cake (see part 1 of the Macchiarini controversy and synthetic trachea transplants for the medical science aspects), a January 5, 2016 Vanity Fair article by Adam Ciralsky documents Macchiarini’s courtship of an NBC ([US] National Broadcasting Corporation) news producer who was preparing a documentary about him and his work,

Macchiarini, 57, is a magnet for superlatives. He is commonly referred to as “world-renowned” and a “super-surgeon.” He is credited with medical miracles, including the world’s first synthetic organ transplant, which involved fashioning a trachea, or windpipe, out of plastic and then coating it with a patient’s own stem cells. That feat, in 2011, appeared to solve two of medicine’s more intractable problems—organ rejection and the lack of donor organs—and brought with it major media exposure for Macchiarini and his employer, Stockholm’s Karolinska Institute, home of the Nobel Prize in Physiology or Medicine. Macchiarini was now planning another first: a synthetic-trachea transplant on a child, a two-year-old Korean-Canadian girl named Hannah Warren, who had spent her entire life in a Seoul hospital. …

Macchiarini had come to Vieira’s [Meredith Vieira, American journalist] attention in September 2012, when she read a front-page New York Times story about the doctor. She turned to [Benita] Alexander, one of her most seasoned and levelheaded producers, to look into a regenerative-medicine story for television.

…

When Alexander and Macchiarini found themselves together in Illinois for a period of weeks in the spring of 2013—brought there by the NBC special—they met frequently for quiet dinners. The trachea transplant on Hannah Warren, the Korean-Canadian girl, was being performed at Children’s Hospital of Illinois, in Peoria, and the procedure was fraught with risks, not least because Macchiarini’s technique was still a work in progress even for adults. (Christopher Lyles, an American who became the second person to receive an artificial trachea, died less than four months after his surgery at Karolinska.) “He’s a brilliant scientist and a great technical surgeon,” said Dr. Richard Pearl, who operated alongside Macchiarini in Illinois. Like others, Pearl described his Italian colleague as a Renaissance man, fluent in half a dozen languages. Another person, who would get to know him through Alexander, compared Macchiarini to “the Most Interesting Man in the World,” the character made famous in Dos Equis beer commercials.

In Peoria, Macchiarini’s medical magic appeared to have its limitations. Hannah Warren died from post-surgical complications less than three months after the transplant. Her anatomy “was much more challenging than we realized,” Pearl recounted. “Scientifically, the operation itself worked. It was just a shame what happened. When you’re doing something for the first time, you don’t have a textbook. It was the hardest operation I’ve ever scrubbed on.”

Then, there was the romance (from the Ciralsky article),

The personal relationship between Alexander and Macchiarini continued to blossom. In June 2013, they flew to Venice for what Alexander called “an incredibly romantic weekend.” Macchiarini bought her red roses and Venetian-glass earrings and took her on a gondola ride under the Bridge of Sighs. Like a pair of teenagers, they attached love locks to the Ponte dell’Accademia bridge, one of them bearing the inscription “B—P 23/6/13, 4 Ever.” Alexander told me that, “when he took me to Venice, we were still shooting the story … He always paid for everything … gifts, expensive dinners, flowers—the works. When it came to money, he was incredibly generous.”

It is a bedrock principle at NBC and every other news organization that journalists must avoid conflicts of interest, real or apparent. Alexander was not oblivious to this. “I knew that I was crossing the line in the sense that it’s a basic and well-understood rule of journalism that you don’t become involved with one of the subjects of your story, because your objectivity could clearly become compromised,” she told me. “I never once thought about him paying for the trip as him ‘buying’ me in some fashion, or potentially using money to influence me, because, from my perspective anyway … that just wasn’t the case. We were just crazy about each other, and I was falling in love.”

Alexander made her way to Stockholm at a later date (from the Ciralsky article),

Macchiarini was in Stockholm to attend to Yesim Cetir, a 25-year-old Turkish woman whose artificial trachea had failed. As Swedish television later reported, “It has taken nearly 100 surgeries to support the cell tissue around the airpipes. Her breathing is bad, and to avoid suffocation, her respiratory tract must be cleansed from mucus every fourth hour. She has now been lying in the hospital for nearly 1,000 days.” NBC’s special would come to include skeptical commentary from Dr. Joseph Vacanti, who questioned the sufficiency of Macchiarini’s research, but Cetir’s post-operative complications were not mentioned.

Prior to the NBC documentary’s (A Leap of Faith) airing, the romance became an engagement (from the Ciralsky article),

Macchiarini proposed to Benita Alexander on Christmas Day 2013, Alexander said. In the months leading up to the airing of A Leap of Faith, in June 2014, Macchiarini and Alexander went on trips to the Bahamas, Turkey, Mexico, Greece, and Italy. They went on shopping sprees and ate their way through Michelin-starred restaurants. Macchiarini even took Alexander and her daughter to meet his mother at her home, in Lucca. “She cooked homemade gnocchi,” Alexander recalled. Macchiarini’s mother shared pictures from the family photo album while her son translated. Emanuela Pecchia, the woman whom Macchiarini had married years earlier, lived only a short distance away. When Macchiarini informed Alexander, during a dinner cruise later that summer, that his divorce had finally come through, she recounted, he gave her an engagement ring.

…

In the months that followed, the doctor and his fiancée began planning their wedding in earnest. They set a date for July 11, 2015, in Rome. But their desire to marry in the Catholic Church was complicated by the fact that she is Episcopalian and divorced. Divorce would have been an issue for Macchiarini as well. However, Alexander said, Macchiarini insisted that he would fix things by visiting his friend and patient in the Vatican.

In October 2014, Alexander recalled, Macchiarini told her that he had met with Pope Francis for four hours and that the Pontiff consented to the couple’s marriage and, in yet another sign of his progressive tenure, vowed to officiate. Alexander said Macchiarini referred to himself as Pope Francis’s “personal doctor” and maintained that in subsequent meetings his patient offered to host the wedding at his summer residence, the Apostolic Palace of Castel Gandolfo.

Shortly after quitting her job in anticipation of her July 2015 wedding to Macchiarini, Alexander learned that Pope Francis who was supposed to officiate was in fact scheduled to be in South America during that time. From the Ciralsky article,

As Alexander would discover with the help of a private investigator named Frank Murphy, virtually every detail Macchiarini provided about the wedding was false. A review of public records in Italy would also seem to indicate that Macchiarini remains married to Emanuela Pecchia, his wife of nearly 30 years. Murphy, who spent 15 years as a Pennsylvania State Police detective, told me, “I’ve never in my experience witnessed a fraud like this, with this level of international flair…. The fact that he could keep all the details straight and compartmentalize these different lives and lies is really amazing.

Ciralsky broaches the question of why someone with Macchiarini’s accomplishments would jeopardize his position in such a way,

To understand why someone of considerable stature could construct such elaborate tales and how he could seemingly make others believe them, I turned to Dr. Ronald Schouten, a Harvard professor who directs the Law and Psychiatry Service at Massachusetts General Hospital. “We’re taught from an early age that when something is too good to be true, it’s not true,” he said. “And yet we ignore the signals. People’s critical judgment gets suspended. In this case, that happened at both the personal and institutional level.” Though he will not diagnose from a distance, Schouten, who is one of the nation’s foremost authorities on psychopathy, observed, “Macchiarini is the extreme form of a con man. He’s clearly bright and has accomplishments, but he can’t contain himself. There’s a void in his personality that he seems to want to fill by conning more and more people.” When I asked how Macchiarini stacks up to, say, Bernie Madoff, he laughed and said, “Madoff was an ordinary con man with a Ponzi scheme. He never claimed to be the chairman of the Federal Reserve. He didn’t suggest he was part of a secret international society of bankers. This guy is really good.”

In addition to the romance, Ciralsky and Vanity Fair checked out Macchiarini’s résumé,

Vanity Fair contacted many of the schools at which Macchiarini claimed to have either earned a degree or held an academic post. While the University of Pisa confirmed that he indeed received an M.D. and had specialized in surgery, the University of Alabama at Birmingham denied that Macchiarini earned a master’s in biostatistics or that he participated in a two-year fellowship in thoracic surgery. In fact, according to U.A.B. spokesman Bob Shepard, the only record the school has for Macchiarini indicates that he did a six-month non-surgical fellowship in hematology/oncology—which according to the current Accreditation Council for Graduate Medical Education guidelines is 30 months shy of what is required for a clinical fellowship in that field. The University of Paris—Sud never responded to repeated requests for comment, but Hannover Medical School wrote to say that Macchiarini had been neither a full nor an associate professor there, merely an adjunct.

Comments

As I noted in part 1, there are medical science and ethical issues to be considered. As well, Macchiarini’s romantic behaviour certainly seems fraudulent as do parts of his curriculum vitae (CV) and there’s more about Macchiarini’s professional accomplishments (read Ciralsky’s entire January 5, 2016 Vanity Fair article for details).

The romantic and CV chicanery may or may not suggest serious problems with Macchiarini’s revolutionary procedure and ethics. History is littered with stories of people who achieved extraordinary advances and were not the most exemplary human beings. Paracelsus, founder of the field of toxicology and an important contributor in the fields of medicine and science, was reputedly a sketchy character. Caravaggio now remembered for his art, killed someone (accidentally or not) and was known for his violent behaviour even in a time when there was higher tolerance for it.

What I’m saying is that Macchiarini may be pioneering something important regardless of how you view his romantic chicanery and falsified CV. Medical research can be high risk and there is no way to avoid that sad fact. However, criticisms of the work from Macchiarini’s colleagues need to be addressed and the charge that a Russian patient who was not in imminent danger and not properly advised of the extremely high risk must also be addressed.

It should also be remembered that Macchiarini did not pull this off by himself. Institutions such as the Karolinska Institute failed to respond appropriately in the initial stages. As well, the venerable medical journal, The Lancet seems reluctant to address the situation even now.

Before dissecting the Alexander situation, it should be said that she showed courage in admitting her professional transgression and discussing a painful and humiliating romantic failure. All of us are capable of misjudgments and wishful thinking, unfortunately for her, this became an international affair.

More critically, Alexander, a journalist, set aside her ethics for a romance and what seems to be surprisingly poor research by Alexander’s team. (Even I had a little something about this in 2013.) How did a crack NBC research team miss the problems? (For the curious, this Bryan Burrough April 30, 2015 article for Vanity Fair highlighting scandals plaguing NBC News may help to answer the question about NBC research.)

Finally, there’s an enormous amount of pressure on stem cell scientists due to the amounts of money and the degree of prestige involved. Ciralsky’s story notes the pressure when he describes how Macchiarini got one of this positions at an Italian facility in Florence through political machinations. (The situation is a little more complicated than I’ve described here but an accommodation in Macchiarini’s favour was made.) Laura Margottini’s Oct. 7, 2014 article for Science magazine provides a synopsis of another stem cell controversy in Italy.

Stem cell controversies have not been confined to Italy or Europe for that matter. There was the South Korean scandal in 2006 (see a Sept. 19, 2011 BBC [British Broadcasting Corporation] news online post for an update and synopsis) when a respected scientist was found to have falsified research results. Up to that point, South Korea was considered the world leader in the field.

Finally, if there are two survivors, is there a possibility that this procedure could be made successful for more patients or that some patients are better candidates than others?

Additional notes

Macchiarini is mounting a defence for himself according to a March 30, 2016 news item on phys.org and a Swedish survey indicates that the average Swede’s trust in researchers still remains high despite the Macchiarini imbroglio according to an April 15, 2016 news item on phys.org.

For anyone interested in the timeline and updates for this scandal, Retraction Watch offers this: http://retractionwatch.com/2016/02/12/reading-about-embattled-trachea-surgeon-paolo-macchiarini-heres-what-you-need-to-know/

Macchiarini controversy and synthetic trachea transplants (part 1 of 2)

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Having featured Paolo Macchiarini and his work on transplanting synthetic tracheas into humans when it was lauded (in an Aug. 2, 2011 post titled: Body parts nanostyle), it seems obligatory to provide an update now that he and his work are under a very large cloud. Some of this is not new, there were indications as early as this Dec. 27, 2013 post titled: Trachea transplants: an update which featured an article by Gretchen Vogel in Science magazine hinting at problems.

Now, a Feb. 4, 2016 article by Gretchen Vogel for Science magazine provides a more current update and opens with this (Note: Links have been removed),

The Karolinska Institute (KI) in Stockholm “has lost its confidence” in surgeon Paolo Macchiarini, a senior researcher at the institute, and will end its ties with him. In a statement issued today, KI said that it won’t renew Macchiarini’s contract after it expires on 30 November 2016.

The move comes in the wake of a chilling three-part TV documentary about Macchiarini, a former media darling who was cleared of scientific misconduct charges by KI vice-chancellor Anders Hamsten last summer. Among other things, The Experiments, broadcast in January by Swedish public television channel SVT, suggests that Macchiarini didn’t fully inform his patients about the risks of his pioneering trachea implants. Most of the patients died, including at least one—a woman treated in Krasnodar, Russia—who was not seriously ill before the surgery.

For a profession that has “do no harm” as one of its universal tenets, the hint that a patient not in dire need agreed to a very risky procedure without being properly apprised of the risks is chilling.

Macchiarini’s behavriour is not the only concern, the Karolinska Institute is also being held to account (from the Vogel article),

The film has also raised questions about the way Hamsten and other administrators at KI, Sweden’s most prestigious university and home of the selection committee for the Nobel Prize in Physiology or Medicine, have handled the scandal. Today [Feb. 4, 2016], the Institute’s Board decided to launch an independent review, to be led by an experienced lawyer, into KI’s 5-year relationship with Macchiarini. Among the things the inquiry should address is whether any errors were made or laws were broken when Macchiarini was hired; whether misconduct charges against him were handled properly; and why, given the controversy, he was given a new 1-year contract as a senior researcher after his appointment as a visiting professor at KI ended in October 2015.

Getting back to Macchiarini (from the Vogel article),

In 2014, colleagues at KI alleged that Macchiarini’s papers made his transplants seem more successful than they were, omitting serious complications. Two patients treated at Karolinska died, and a third has been in intensive care since receiving a trachea in 2012. The Illinois patient also died, as did three patients in Russia. Bengt Gerdin, a professor emeritus of surgery at Uppsala University in Sweden who investigated the charges at KI’s request, concluded in May 2015 that differences between published papers and lab records constituted scientific misconduct. But Hamsten rejected that conclusion in August, based on additional material Macchiarini submitted later.

The documentary shows footage of a patient who says Macchiarini reassured him before the surgery that experiments had been done on pigs, when in fact none had taken place. It also follows the wrenching story of the first patient in Krasnodar. A 33-year-old woman, she was living with a tracheostomy that she said caused her pain, but her condition was not life-threatening. The film suggests that she wasn’t fully aware of the risks of the operation, and that Macchiarini and his colleagues knew about problems with the implant before the surgery. The patient’s first implant failed, and she received a second one in 2013. She died in 2014.

So in May 2015, an investigator concluded there had been scientific misconduct and, yet, Macchiarini’s contract is renewed in the fall of 2015.

Kerry Grens in a March 7, 2016 article for The Scientist provides information about the consequences of the latest investigation into Macchiarini’s work (Note: Links have been removed),

Karl-Henrik Grinnemo, a surgeon at the Karolinska Institute and one of a number of colleagues who voiced concerns about the conduct of fellow surgeon Paolo Macchiarini, is no longer a coauthor on a 2011 The Lancet study led by Macchiarini that described an artificial windpipe. Grinnemo asked to be removed from the paper, and the journal complied last week (March 3).

Grinnemo’s removal from the study is the latest in a string of repercussions related to an investigation of Macchiarini’s work. Last month, the head of the Karolinska Institute, Anders Hamsten, resigned because the institution’s initial investigation concluded no wrongdoing. Hamsten said he and his colleagues were probably wrong about Macchiarini; the institute has launched another investigation into the surgeon’s work.

A March 23, 2016 news item on phys.org announces Macchiarini’s firing from the Karolinska Institute and provides a brief description of his work with synthetic tracheas (Note: A link has been removed),

Sweden’s Karolinska Institute (KI), which awards the Nobel Prize for Medicine, on Wednesday [March 23, 2016] dismissed a Italian transplant surgeon suspected of research fraud and ethical breaches, in an affair that has plunged the renowned institution into crisis.

“It is impossible for KI to continue to have any cooperation with Paolo Macchiarini. He has acted in a way that has had very tragic consequences for the people affected and their families. His conduct has seriously damaged confidence in KI,” human resource director Mats Engelbrektson said in a statement.

Macchiarini, a 57-year-old visiting professor at Karolinska since 2010, rose to fame for carrying out the first synthetic trachea, or windpipe, transplant in 2011.

It was a plastic structure seeded with the patient’s own stem cells—immature cells that grow into specialised cells of the body’s organs.

The surgeon performed three such operations in Stockholm and five others around the world, and the exploit was initially hailed as a game-changer for transplant medicine.

But six of the eight patients reportedly died, and allegations ensued that the risky procedure had been carried out on at least one individual who had not been life-threateningly ill.

Macchiarini is also suspected of lying about his scientific research and his past experience with prestigious medical research centres.

“Paolo Macchiarini supplied false or misleading information in the CV he submitted to KI” and “demonstrated scientific negligence” in his research, said the institute.

H/t to Don Bright, a reader who informed me about this April 2, 2016 posting by Pierre Delaere (a long time Macchiarini critic), published in Leonid Schneider’s blog, For Better Science,

I have written this overview as a trachea surgeon working at KU Leuven and privileged witness of the “Tracheal regeneration scandal” from the very start.

Because of its immense scale, the scandal is difficult to grasp and explain. Fortunately, we have recently been provided with an excellent overview in the 3 x 1-hour documentary by Bosse Lindquist on Swedish national TV. Due to Paolo Macchiarini’s appetite for the spotlights and thanks to the professional standards of the Swedish top producer this is probably the very first case of a medical crime played out in the media. Anyone who has seen this brilliant investigative documentary cannot help but wonder why there are still people who doubt that this is a case of gross medical misconduct.

The story began in Barcelona in 2008 with the publication in The Lancet of a report on a regenerated windpipe, featuring Paolo Macchiarini (PM) as its first author (Macchiarini et al. Lancet 2008). This ground-breaking achievement consisted of bringing to life a dead windpipe from a donor, by putting it in a plastic box, a so-called ‘bioreactor’ together with bone marrow fluid (stem cells). A few weeks later, I wrote a letter to The Lancet, pointing out:

“The main drawback of the proposed reconstruction is the lack of an intrinsic blood supply to the trachea. We know that a good blood supply is the first requirement in all other tissue and organ transplantations. Therefore, the reported success of this technique is questionable” (correspondence by Delaere and Hermans, Lancet 2009).

Delaere goes on to recount and critique the story of the first synthetic trachea,

… PM had mounted bone marrow extract (‘stem cells’) on a plastic tube (‘bioartificial trachea’) in a plastic box (‘bioreactor’). After a day or two this creation was ‘successfully’ transplanted in a patient with a trachea defect. This occurred in the Karolinska hospital in July 2011 and was reported on in The Lancet shortly afterwards . Biologically speaking, the procedure is absolutely implausible.

In reality an important part of the windpipe had been replaced by a synthetic tube, and the presence of stem cells made no difference to this whatsoever.

For those not in the field, this procedure may still seem acceptable. A blood vessel can also be replaced by synthetic material because the material can grow into the sterile environment of the blood stream. However, this is completely impossible if the synthetic material is exposed to an environment of inhaled air full of bacteria. The laws of biology allow us to predict accurately what will happen after part of the windpipe has been replaced by a synthetic tube. After some time, the suturing between the synthetic tube and the surrounding tissue will come loose, leading to a number of serious complications. These complications inevitably lead to death in the short (months) or in the mid-long term (a few years). How long the patient will survive also depends on the options still left to treat complications. In most cases so far, a metal stent had to be implanted to keep the airway open in the sutured area.It is entirely predictable that additional complications after placement of the metal stent will ultimately lead to the patient’s death, usually by asphyxiation or by bleeding out after complete rupture of the sutures. This gruesome fate awaiting patients was clearly shown in the documentary. Replacing a part of the trachea by a synthetic tube can therefore be compared to death by medical torture. The amount of suffering it induces is directly proportional to the duration between implantation and the patient’s death.

Delaere describes his own and others’ efforts to bring these issues to light,

Since 2011, I have contacted both the President of KI and the Editors of The Lancet with well-documented information to clarify that what had happened was completely unacceptable. These alerts were repeated in 2013 and 2014. Since 2014, four doctors from KI, who had seen it all happen, have been collecting evidence to show the extent of misconduct [Matthias Corbascio, Thomas Fux, Karl-Henrik Grinnemo and Oscar Simonsson, their letter to Vice-Chancellor Hamsten from June 22, 2015, and its attachments available here; -LS]. Not only did KI not react to the doctors’ complaint, these doctors were in fact intimidated and threatened with dismissal. KI’s Ethical Commission came to a verdict of ‘no misconduct’ in April 2015 following an inquiry based on a series of complaints filed by myself [verdict available from SVT here, -LS]. The Lancet Editor did not even bother to reply to my complaints.

In the reports, eight patients were given synthetic tracheas with six now dead and, allegedly, two still living. Delaere comments,

… To prove that this transplantation technique is effective, reports about the long-term success of this technique in the first 2 patients in Barcelona and London is still being spread. What the real situation of the two patients is at the moment is very difficult to establish. For some time now, reports about these two cases seem to have disappeared from the face of the earth. After the air has been cleared in Sweden, the same will probably happen in London and Barcelona.

Comments

Sometimes medical research can be very dangerous. While, a 25% chance of success (two of Macchiarini’s eight patients undergoing the synthetic trachea transplant have allegedly survived) is not encouraging, it’s understandable that people in dire circumstances and with no other options might want to take a chance.

It’s troubling that the woman in Russia was not in dire straights and that she may not have known how dangerous the procedure is. It would have been unethical of Macchiarini to knowingly perform the procedure under those circumstances.

I am wrestling with some questions about the composite used to create the synthetic trachea and the surviving patients. My understanding is that the composite was designed for eventual deterioration as the patient’s own harvested stem cells fully formed the trachea. Whether the trachea is the one I imagined or he plastic one described by Delaere, how did two patients survive and what is their condition now? The first patient Andemariam Teklesenbet Beyene in 2011 had apparently completed his PhD studies by 2013 (my Dec. 27, 2013 posting). Assuming Beyene is one of the two survivors, what has happened to him and the other one?

As for Delaere’s comments, he certainly raises some red flags not only regarding the procedure but the behaviour of the Lancet editorial team and the Karolinska Institute (they seem to be addressing the issues by firing Macchiarini and with the resignations of the staff and board).

There are two more twists to this story, which carries on in part 2.

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