Tag Archives: University of Pennsylvania

3D printing method makes band-aids for your heart

Matthew Davidson, a Research Associate with the University of Colorado demonstrates a 3D printed biomaterials for use inside the body including bandages that could be put on a beating human heart in Jason Burdick’s lab. (Photo by Casey A. Cass/University of Colorado)

Soft, strong, and flexible, that’s what you need if you’re going to apply a bandage to a heart and according to an August 1, 2024 news item on phys.org, researchers have developed a promising new material,

In the quest to develop life-like materials to replace and repair human body parts, scientists face a formidable challenge: Real tissues are often both strong and stretchable and vary in shape and size.

A CU [Colorado University] Boulder-led team, in collaboration with researchers at the University of Pennsylvania, has taken a critical step toward cracking that code. They’ve developed a new way to 3D print material that is at once elastic enough to withstand a heart’s persistent beating, tough enough to endure the crushing load placed on joints, and easily shapable to fit a patient’s unique defects.

Better yet, it sticks easily to wet tissue.

Their breakthrough, described in the Aug. 2 [2024] edition of the journal Science, helps pave the way toward a new generation of biomaterials, from internal bandages that deliver drugs directly to the heart to cartilage patches and needle-free sutures.

An August 1, 2024 University of Colorado at Boulder news release (also on EurekAlert) by Lisa Marshall and Nicholas Goda, which originated the news item, provides more detail about the research and the challenges, Note: A link has been removed,

“Cardiac and cartilage tissues are similar in that they have very limited capacity to repair themselves. When they’re damaged, there is no turning back,” said senior author Jason Burdick, a professor of chemical and biological engineering at CU Boulder’s BioFrontiers Institute. “By developing new, more resilient materials to enhance that repair process, we can have a big impact on patients.”

Worm ‘blobs’ as inspiration

Historically, biomedical devices have been created via molding or casting, techniques which work well for mass production of identical implants but aren’t practical when it comes to personalizing those implants for specific patients. In recent years, 3D printing has opened a world of new possibilities for medical applications by allowing researchers to make materials in many shapes and structures.

Unlike typical printers, which simply place ink on paper, 3D printers deposit layer after layer of plastics, metals or even living cells to create multidimensional objects.

One specific material, known as a hydrogel (the stuff that contact lenses are made of), has been a favorite prospect for fabricating artificial tissues, organs and implants.

But getting these from the lab to the clinic has been tough because traditional 3D-printed hydrogels tend to either break when stretched, crack under pressure or are too stiff to mold around tissues.

“Imagine if you had a rigid plastic adhered to your heart. It wouldn’t deform as your heart beats,” said Burdick. “It would just fracture.”

To achieve both strength and elasticity within 3D printed hydrogels, Burdick and his colleagues took a cue from worms, which repeatedly tangle and untangle themselves around one another in three-dimensional “worm blobs” that have both solid and liquid-like properties. Previous research has shown that incorporating similarly intertwined chains of molecules, known as “entanglements,” can make them tougher.

Their new printing method, known as CLEAR (for Continuous-curing after Light Exposure Aided by Redox initiation), follows a series of steps to entangle long molecules inside 3D-printed materials much like those intertwined worms.

When the team stretched and weight-loaded those materials in the lab (one researcher even ran over a sample with her bike) they found them to be exponentially tougher than materials printed with a standard method of 3D printing known as Digital Light Processing (DLP). Better yet: They also conformed and stuck to animal tissues and organs.

“We can now 3D print adhesive materials that are strong enough to mechanically support tissue,” said co-first author Matt Davidson, a research associate in the Burdick Lab. “We have never been able to do that before.”

Revolutionizing care

Burdick imagines a day when such 3D-printed materials could be used to repair defects in hearts, deliver tissue-regenerating drugs directly to organs or cartilage, restrain bulging discs or even stitch people up in the operating room without inflicting tissue damage like a needle and suture can.

His lab has filed for a provisional patent and plans to launch more studies soon to better understand how tissues react to the presence of such materials.

But the team stresses that their new method could have impacts far beyond medicine—in research and manufacturing too. For instance, their method eliminates the need for additional energy to cure, or harden, parts, making the 3D printing process more environmentally friendly.

“This is a simple 3D processing method that people could ultimately use in their own academic labs as well as in industry to improve the mechanical properties of materials for a wide variety of applications,” said first author Abhishek Dhand, a researcher in the Burdick Lab and doctoral candidate in the Department of Bioengineering at the University of Pennsylvania. “It solves a big problem for 3D printing.”

Here’s a link to and a citation for the paper,

Additive manufacturing of highly entangled polymer networks by Abhishek P. Dhand, Matthew D. Davidson, Hannah M. Zlotnick, Thomas J. Kolibaba, Jason P. Killgore, and Jason A. Burdick. Science 1 Aug 2024 Vol 385, Issue 6708 pp. 566-572 DOI: 10.1126/science.adn692

This paper is behind a paywall.

Credibility slips according to US survey on public perceptions of scientists

Figure 1. Perceptions of scientists’ credibility. [downloaded from https://www.annenbergpublicpolicycenter.org/annenberg-survey-finds-public-perceptions-of-scientists-credibility-slips/]

A June 26, 2024 news item on ScienceDaily describes the research, which resulted in the graphic you see in the above,

New analyses from the Annenberg Public Policy Center find that public perceptions of scientists’ credibility — measured as their competence, trustworthiness, and the extent to which they are perceived to share an individual’s values — remain high, but their perceived competence and trustworthiness eroded somewhat between 2023 and 2024. The research also found that public perceptions of scientists working in artificial intelligence (AI) differ from those of scientists as a whole.

A June 26, 2024 Annenberg Public Policy Center of the University of Pennsylvania news release (also on EurekAlert and also received by email), which originated the news item, describes a series of surveys, how the information was gathered, and offers more detail about he results, Note 1: All links removed; Note 2: You can find links and citations for papers mentioned in the news release at the end of this posting.

From 2018-2022, the Annenberg Public Policy Center (APPC) of the University of Pennsylvania relied on national cross-sectional surveys to monitor perceptions of science and scientists. In 2023-24, APPC moved to a nationally representative empaneled sample to make it possible to observe changes in individual perceptions.

The February 2024 findings, released today to coincide with the address by National Academy of  Sciences President Marcia McNutt on “The State of the Science,” come from an analysis of responses from an empaneled national probability sample of U.S. adults surveyed in February 2023 (n=1,638 respondents), November 2023 (n=1,538), and February 2024 (n=1,555).

Drawing on the 2022 cross-sectional data, in an article titled “Factors Assessing Science’s Self-Presentation model and their effect on conservatives’ and liberals’ support for funding science,” published in Proceedings of the National Academy of Sciences (September 2023), Annenberg-affiliated researchers Yotam Ophir (State University of New York at Buffalo and an APPC distinguished research fellow), Dror Walter (Georgia State University and an APPC distinguished research fellow), and Patrick E. Jamieson and Kathleen Hall Jamieson of the Annenberg Public Policy Center isolated factors that underlie perceptions of scientists (Factors Assessing Science’s Self-Presentation, or FASS). These factors predict public support for increased funding of science and support for federal funding of basic research.

The five factors in FASS are whether science and scientists are perceived to be credible and prudent, and whether they are perceived to overcome bias, correct error (self-correcting), and whether their work benefits people like the respondent and the country as a whole (beneficial). In a 2024 publication titled “The Politicization of Climate Science: Media Consumption, Perceptions of Science and Scientists, and Support for Policy” (May 26, 2024) in the Journal of Health Communication, the same team showed that these five factors mediate the relationship between exposure to media sources such as Fox News and outcomes such as belief in anthropogenic climate change, perception of the threat it poses, and support for climate-friendly policies such as a carbon tax.

Speaking about the FASS model, Jamieson, director of the Annenberg Public Policy Center and director of the survey, said that “because our 13 core questions reliably reduce to five factors with significant predictive power, the ASK survey’s core questions make it possible to isolate both stability and changes in public perception of science and scientists across time.” (See the appendix for the list of questions.)

The new research finds that while scientists are held in high regard, two of the three dimensions that make up credibility – perceptions of competence and trustworthiness – showed a small but statistically significant drop from 2023 to 2024, as did both measures of beneficial. The 2024 survey data also indicate that the public considers AI scientists less credible than scientists in general, with notably fewer people saying that AI scientists are competent and trustworthy and “share my values” than scientists generally.

“Although confidence in science remains high overall, the survey reveals concerns about AI science,” Jamieson said. “The finding is unsurprising. Generative AI is an emerging area of science filled with both great promise and great potential peril.”

The data are based on Annenberg Science Knowledge (ASK) waves of the Annenberg Science and Public Health (ASAPH) surveys conducted in 2023 and 2024. The findings labeled 2023 are based on a February 2023 survey, and the findings labeled 2024 are based on combined ASAPH survey half-samples surveyed in November 2023 and February 2024.

For further details, download the toplines and a series of figures that accompany this summary.

Perceptions of scientists overall

In the FASS model, perceptions of scientists’ credibility are assessed through perceptions of whether scientists are competent, trustworthy, and “share my values.” The first two of those values slipped in the most recent survey. In 2024, 70% of those surveyed strongly or somewhat agree that scientists are competent (down from 77% in 2023) and 59% strongly or somewhat agree that scientists are trustworthy (down from 67% in 2023). (See figure 1 [see the first item in this post], and figs. 2-4 for other findings.)

The survey also found that in 2024, fewer people felt that scientists’ findings benefit “the country as a whole” and “benefit people like me.” In 2024, 66% strongly or somewhat agreed that findings benefit the country as a whole (down from 75% in 2023). Belief that scientists’ findings “benefit people like me,” also declined, to 60% from 68%. Taken together those two questions make up the beneficial factor of FASS. (See fig. 5.)

The findings follow sustained attacks on climate and Covid-19-related science and, more recently, public concerns about the rapid development and deployment of artificial intelligence.

Comparing perceptions of scientists in general with climate and AI scientists

Credibility: When asked about three factors underlying scientists’ credibility, AI scientists have lower credibility in all three values. (See fig. 6.)

  • Competent: 70% strongly/somewhat agree that scientists are competent, but only 62% for climate scientists and 49% for AI scientists.
  • Trustworthy: 59% agree scientists are trustworthy, 54% agree for climate scientists, 28% for AI scientists.
  • Share my values: A higher number (38%) agree that climate scientists share my values than for scientists in general (36%) and AI scientists (15%). More people disagree with this for AI scientists (35%) than for the others.

Prudence: Asked whether they agree or disagree that science by various groups of scientists “creates unintended consequences and replaces older problems with new ones,” over half of those surveyed (59%) agree that AI scientists create unintended consequences and just 9% disagree. (See fig. 7.)

Overcoming bias: Just 42% of those surveyed agree that scientists “are able to overcome human and political biases,” but only 21% feel that way about AI scientists. In fact, 41% disagree that AI scientists are able to overcome human political biases. In another area, just 23% agree that AI scientists provide unbiased conclusions in their area of inquiry and 38% disagree. (See fig. 8.)

Self-correction: Self-correction, or “organized skepticism expressed in expectations sustaining a culture of critique,” as the FASS paper puts it, is considered by some as a “hallmark of science.” AI scientists are seen as less likely than scientists or climate scientists to take action to prevent fraud; take responsibility for mistakes; or to have mistakes that are caught by peer review. (See fig. 9.)

Benefits: Asked about the benefits from scientists’ findings, 60% agree that scientists’ “findings benefit people like me,” though just 44% agree for climate scientists and 35% for AI scientists. Asked about whether findings benefit the country as a whole, 66% agree for scientists, 50% for climate scientists and 41% for AI scientists. (See fig. 10.)

Your best interest: The survey also asked respondents how much trust they have in scientists to act in the best interest of people like you. (This specific trust measure is not a part of the FASS battery.) Respondents have less trust in AI scientists than in others: 41% have a great deal/a lot of trust in medical scientists; 39% in climate scientists; 36% in scientists; and 12% in AI scientists. (See fig. 11.)

The data from ASK surveys have been used to date in four peer-reviewed papers:

  • Using 2019 ASK data: Jamieson, K. H., McNutt, M., Kiermer, V., & Sever, R. (2019). Signaling the trustworthiness of science. Proceedings of the National Academy of Sciences, 116(39), 19231-19236.
  • Using 2022 ASK data: Ophir, Y., Walter, D., Jamieson, P. E., & Jamieson, K. H. (2023). Factors Assessing Science’s Self-Presentation model and their effect on conservatives’ and liberals’ support for funding science. Proceedings of the National Academy of Sciences, 120(38), e2213838120.
  • Using  2024 ASK data: Lupia, A., Allison, D. B., Jamieson, K. H., Heimberg, J., Skipper, M., & Wolf, S. M. (2024). Trends in US public confidence in science and opportunities for progress. Proceedings of the National Academy of Sciences, 121(11), e2319488121. 
  • Using Nov 2023 and Feb 2024 ASK data: Ophir, Y., Walter, D., Jamieson, P. E., & Jamieson, K. H. (2024). The politicization of climate science: Media consumption, perceptions of science and scientists, and support for policy. Journal of Health Communication, 29(sup1): 18-27.
     

APPC’s ASAPH survey

The survey data come from the 17th and 18th waves of a nationally representative panel of U.S. adults, first empaneled in April 2021, conducted for the Annenberg Public Policy Center by SSRS, an independent market research company. These waves of the Annenberg Science and Public Health (ASAPH) knowledge survey were fielded February 22-28, 2023, November 14-20, 2023, and February 6-12, 2024, and have margins of sampling error (MOE) of ± 3.2, 3.3 and 3.4 percentage points at the 95% confidence level. In November 2023, half of the sample was asked about “scientists” and the other half “climate scientists.” In February 2024, those initially asked about “scientists” were asked about “scientists studying AI” and the other half “scientists.” This provided two half samples addressing specific areas of study, while all panelists were asked about “scientists” generally. All figures are rounded to the nearest whole number and may not add to 100%. Combined subcategories may not add to totals in the topline and text due to rounding.

The policy center has been tracking the American public’s knowledge, beliefs, and behaviors regarding vaccination, Covid-19, flu, maternal health, climate change, and other consequential health issues through this survey panel for over three years. In addition to Jamieson, the APPC team includes Shawn Patterson Jr., who analyzed the data; Patrick E. Jamieson, director of the Annenberg Health and Risk Communication Institute, who developed the questions; and Ken Winneg, managing director of survey research, who supervised the fielding of the survey.

Here are links to and citations for the papers listed above in the June 26, 2024 news release,

Using 2019 ASK data: Signaling the trustworthiness of science by Kathleen Hall Jamieson, Marcia McNutt, Veronique Kiermer, and Richard Sever.. Proceedings of the National Academy of Sciences (PNAS), 116 (39), 19231-19236 September 23, 2019 DOI: https://doi.org/10.1073/pnas.1913039116

Using 2022 ASK data Factors Assessing Science’s Self-Presentation model and their effect on conservatives’ and liberals’ support for funding science by Yotam Ophir, Dror Walter, Patrick E. Jamieson, and Kathleen Hall Jamieson.. Proceedings of the National Academy of Sciences (PNAS), 120 (38), e2213838120 September 11, 2023 DOI: https://doi.org/10.1073/pnas.2213838120

Using  2024 ASK data: Trends in US public confidence in science and opportunities for progress by Arthur Lupia, David B. Allison, Kathleen Hall Jamieson, Jennifer Heimberg, Magdalena Skipper, and Susan M. Wolf.. Proceedings of the National Academy of Sciences (PNAS), 121 (11), e2319488121 March 4, 2024 DOI: https://doi.org/10.1073/pnas.2319488121 

Using Nov 2023 and Feb 2024 ASK data: The politicization of climate science: Media consumption, perceptions of science and scientists, and support for policy by by Yotam Ophir, Dror Walter, Patrick E. Jamieson & Kathleen Hall Jamieson.. Journal of Health Communication, 29 (sup1): 18-27 DOI: https://doi.org/10.1080/10810730.2024.2357571 Published online: 26 May 2024

The 2019 paper ‘Signaling …’ has been featured here before in a September 30, 2019 posting, “Do you believe in science?” In addition to some of my comments, I embedded Adam Lambert’s version of Cher’s song ‘Do You Believe in Love?’ where you’ll see Cher brush away a few tears as she listens to her dance hit made love ballad.

The 2024 paper ‘Trends ..’ has also been featured here, albeit briefly, in an April 8, 2024 posting, “Trust in science remains high but public questions scientists’ adherence to science’s norms.”

Trust in science remains high but public questions scientists’ adherence to science’s norms

A March 4, 2024 Annenberg Public Policy Center of the University of Pennsylvania news release (also on EurekAlert and received via email) announces research into public trust in science in the US,

Science is one of the most highly regarded institutions in America, with nearly three-quarters of the public expressing “a great deal” or “a fair amount” of confidence in scientists. But confidence in science has nonetheless declined over the past few years, since the early days of the Covid-19 pandemic, as it has for most other major social institutions.

In a new article, members of the Strategic Council of the National Academies of Sciences, Engineering, and Medicine [NASEM] examine what has happened to public confidence in science, why it has happened, and what can be done to elevate it. The researchers write that while there is broad public agreement about the values that should underpin science, the public questions whether scientists actually live up to these values and whether they can overcome their individual biases.

The paper, published in the Proceedings of the National Academy of Sciences (PNAS), relies in part on new data being released in connection with this article by the Annenberg Public Policy Center (APPC) of the University of Pennsylvania. The data come from the Annenberg Science Knowledge (ASK) survey conducted February 22-28, 2023, with an empaneled, nationally representative sample of 1,638 U.S. adults who were asked about their views on scientists and science. The margin of error for the entire sample is ± 3.2 percentage points at the 95% confidence level. (See the paper for the findings.) The survey is directed by APPC director Kathleen Hall Jamieson, a member of the Strategic Council and a co-author of the PNAS paper.

Decline in confidence comparable to other institutions

The researchers also examine trends in public confidence in science dating back 20 years from other sources, including the Pew Research Center and the General Social Survey of National Opinion Research at the University of Chicago. These show a recent decline consistent with the decline seen for other institutions.

“We’re of the view that trust has to be earned,” said lead author Arthur Lupia, a member of the NASEM’s Strategic Council for Research Excellence, Integrity, and Trust, and associate vice president for research at the University of Michigan. “We wanted to understand how trust in science is changing, and why, and is there anything that the scientific enterprise can do to regain trust?”

Highlights

“Confidence in science is high relative to nearly all other civic, cultural, and government institutions…,” the article states. In addition:

  • The public has high levels of confidence in scientists’ competence, trustworthiness, and honesty – 84% of survey respondents in February 2023 are very or somewhat confident that scientists provide the public with trustworthy information in the scientists’ area of inquiry.
  • Many in the public question whether scientists share their values and whether scientists can overcome their own biases. For instance, when asked whether scientists will or will not publish findings if a study’s results run counter to the interests of the organization running the study, 70% said scientists will not publish the findings.
  • The public has “consistent beliefs about how scientists should act and beliefs that support their confidence in science despite their concerns about scientists’ possible biases and distortive incentives.” For example, 84% of U.S. adults say it is somewhat or very important for scientists to disclose their funders and 92% say it is somewhat or very important that scientists be open to changing their minds based on new evidence.
  • However, when asked about scientists’ biases, just over half of U.S. adults (53%) say scientists provide the public with unbiased conclusions about their area of inquiry and just 42% say scientists generally are “able to overcome their human and political biases.”

Beyond measurements of trust in science

The Annenberg Public Policy Center’s ASK survey in February 2023 asked U.S. adults more nuanced questions about attitudes toward scientists.

“We’ve developed measures beyond trust or confidence in science in order to understand why some in the public are less supportive of science and scientists than others,” said Jamieson, who is also a professor of communication at the University of Pennsylvania’s Annenberg School for Communication. “Perceptions of whether scientists share one’s values, overcome their human and political biases, and correct mistakes are important as well.”

The ASK survey of U.S. adults found, for instance, that 81% regard scientists as competent, 70% as trustworthy, and 68% as honest, but only 42% say scientists “share my values.”

A more detailed analysis of the variables and effects seen in Annenberg’s surveys was published in September 2023 in PNAS in the paper “Factors Assessing Science’s Self-Presentation model and their effect on conservatives’ and liberals’ support for funding science.”

Confidence in science and Covid-19 vaccination status

The research published in PNAS was initiated by members of the NASEM’s Strategic Council for Research Excellence, Integrity, and Trust, which was established in 2021 to advance the integrity, ethics, resilience, and effectiveness of the research enterprise.

Lupia said the Strategic Council’s conversations about whether trust in science was declining and if so, why, began during the pandemic. “There was great science behind the Covid-19 vaccine, so why was the idea of people taking it so controversial?” he asked. “Covid deaths were so visible and yet the controversy over the vaccine was also so visible – kind of an icon of the public-health implications of declining trust in science.”

The article cites research from the Annenberg Public Policy Center that found important relationships between science-based forms of trust and the willingness to take a Covid-19 vaccine. Data from waves of another APPC survey of U.S. adults in five swing states during the 2020 campaign season – reported in a 2021 article in PNAS – showed that from July 2020 to February 2021, U.S. adults’ trust in health authorities was a significant predictor of the reported intention to get the Covid-19 vaccine. See the article “The role of non-COVID-specific and COVID-specific factors in predicting a shift in willingness to vaccinate: A panel study.”

How to raise confidence in science

Raising public confidence in science, the researchers write, “should not be premised on the assumption that society would be better off with higher levels of uncritical trust in the scientific community. Indeed, uncritical trust in science would violate the scientific norm of organized skepticism and be antithetical to science’s culture of challenge, critique, and self-correction.”

“Instead,” they propose, “researchers, scientific organizations, and the scientific community writ large need to redouble their commitment to conduct, communicate, critique, and – when error is found or misconduct detected – correct the published record in ways that both merit and earn public confidence.”

The data cited in the paper, they conclude, “suggest that the scientific community’s commitment to core values such as the culture of critique and correction, peer review, acknowledging limitations in data and methods, precise specification of key terms, and faithful accounts of evidence in every step of scientific practice and in every engagement with the public may help sustain confidence in scientific findings.”

“Trends in U.S. Public Confidence in Science and Opportunities for Progress” was published March 4, 2024, in PNAS. In addition to Jamieson and Lupia, the authors are David B. Allison, dean of the School of Public Health, Indiana University; Jennifer Heimberg, of the National Academies of Sciences, Engineering, and Medicine; Magdalena Skipper, editor-in-chief of the journal Nature; and Susan M. Wolf, of the University of Minnesota Law and Medical Schools. Allison is co-chair of the National Academies’ Strategic Council; Lupia, Jamieson, Skipper, and Wolf are members of the Council, and Heimberg is the director of the Council.

Here’s a link to and a citation for the paper,

Trends in U.S. public confidence in science and opportunities for progress by Arthur Lupia, David B. Allison, Kathleen Hall Jamieson, and Susan M. Wolf. PNAS March 4, 2024 121 (11) e2319488121 DOI: https://doi.org/10.1073/pnas.2319488121

This paper is open access.

2023 Nobel prizes (medicine, physics, and chemistry)

For the first time in the 15 years this blog has been around, the Nobel prizes awarded in medicine, physics, and chemistry all are in areas discussed here at one or another. As usual where people are concerned, some of these scientists had a tortuous journey to this prestigious outcome.

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.

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 28th and 29th 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.

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),

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.

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,

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.

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

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!

The art and science of architecture that is ‘living-like’

Biology in the service of architecture, from a June 21, 2023 news item on phys.org, Note: Links have been removed,

“This technology is not alive,” says Laia Mogas-Soldevila. “It is living-like.”

The distinction is an important one for the assistant professor at the Stuart Weitzman School of Design [University of Pennsylvania], for reasons both scientific and artistic. With a doctorate in biomedical engineering, several degrees in architecture, and a devotion to sustainable design, Mogas-Soldevila brings biology to everyday life, creating materials for a future built halfway between nature and artifice.

A June 21, 2023 University of Pennsylvania news release (from a Penn Engineering Today blog posting by Devorah Fischler; also on EurekAlert), which originated the news item, provides more details, Note: Links have been removed,

The architectural technology she describes is unassuming at first look: A freeze-dried pellet, small enough to get lost in your pocket. But this tiny lump of matter, the result of more than a year’s collaboration between designers, engineers and biologists, is a biomaterial that contains a “living-like” system.

When touched by water, the pellet activates and expresses a glowing protein, its fluorescence demonstrating that life and art can harmonize into a third and very different thing, as ready to please as to protect. Woven into lattices made of flexible natural materials promoting air and moisture flow, the pellets form striking interior design elements that could one day keep us healthy.

“We envision them as sensors,” explains Mogas-Soldevila. “They may detect pathogens, such as bacteria or viruses, or alert people to toxins inside their home. The pellets are designed to interact with air. With development, they could monitor or even clean it.”

For now, they glow, a triumphant first stop on the team’s roadmap to the future. The fluorescence establishes that the lab’s biomaterial manufacturing process is compatible with the leading-edge cell-free engineering that gives the pellets their life-like properties.

A rapidly expanding technology, cell-free protein expression systems allow researchers to manufacture proteins without the use of living cells.

Gabrielle Ho, Ph.D. candidate in the Department of Bioengineering and co-leader of the project, explains how the team’s design work came to be cell-free, a technique rarely explored outside of lab study or medical applications.

“Typically, we’d use living E. coli cells to make a protein,” says Ho. “E. coli is a biological workhorse, accessible and very productive. We’d introduce DNA to the cell to encourage expression of specific proteins. But this traditional method was not an option for this project. You can’t have engineered E. coli hanging on your walls.”

Cell-free systems contain all the components a living cell requires to manufacture protein —energy, enzymes and amino acids — and not much else. These systems are therefore not alive. They do not replicate, and neither can they cause infection. They are “living-like,” designed to take in DNA and push out protein in ways that previously were only possible using living cells.

“One of the nicest things about these materials not being alive,” says Mogas-Soldevila, “is that we don’t need to worry about keeping them that way.”

Unlike living cells, cell-free materials don’t need a wet environment or constant monitoring in a lab. The team’s research has established a process for making these dry pellets that preserves bioactivity throughout manufacturing, storage and use.

Bioactive, expressive and programmable, this technology is designed to capitalize on the unique properties of organic materials.

Mogas-Soldevila, whose lab focuses exclusively on biodegradable architecture, understands the value of biomaterials as both environmentally responsible and aesthetically rich.

“Architects are coming to the realization that conventional materials — concrete, steel, glass, ceramic, etc. — are environmentally damaging and they are becoming more and more interested in alternatives to replace at least some of them. Because we use so much, even being able to replace a small percentage would result in a significant reduction in waste and pollution.”

Her lab’s signature materials — biopolymers made from shrimp shells, wood pulp, sand and soil, silk cocoons, and algae gums — lend qualities over and above their sustainable advantages.

“My obsession is diagnostic, but my passion is playfulness,” says Mogas-Soldevila. “Biomaterials are the only materials that can encapsulate this double function observed in nature.”

This multivalent approach benefited from the help of Penn Engineering’s George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, and the support of its director, Sevile Mannickarottu. In addition to contributing essential equipment and research infrastructure to the team, Mannickarottu was instrumental in enabling the interdisciplinary relationships that led the team to success, introducing Ho to the DumoLab Research team collaborators. These include Mogas-Soldevila, Camila Irabien, a Penn Biology major who provided crucial contributions to experimental work, and Fulbright design fellow Vlasta Kubušová, who co-led the project during her time at Penn and who will continue fueling the project’s next steps.

The cell-free manufacturing and design research required unique dialogues between science and art, categories that Ho believed to be entirely separate before embarking on this project.

“I learned so much from the approach the designers brought to the lab,” says Ho. “Usually, in science, we have a specific problem or hypothesis that we systematically work towards.”

But in this collaboration, things were different. Open-ended. The team sought a living-like platform that does sensing and tells people about interactive matter. They needed to explore, step by step, how to get there.

“Design is only limited by imagination. We sought a technology that could help build towards a vision, and that turned out to be cell-free” says Ho.

“For my part,” says Mogas-Soldevila, “it was inspiring to witness the rigor and attention to constraints that bioengineering brings.”

The constraints were many — machine constraints, biological constraints, financial constraints and space constraints.

“But as we kept these restrictions in play,” she continues, “we asked our most pressing creative questions. Can materials warn us of invisible threats? How will humans react to these bioactive sites? Will they be beautiful? Will they be weird? Most importantly, will they enable a new aesthetic relationship with the potential of bio-based and bioactive matter?”

Down the line, the cell-free pellets and biopolymer lattices could drape protectively over our interior lives, caring for our mental and physical health. For now, research is ongoing, the poetry of design energized by constraint, the constraint of engineering energized by poetry. [emphases mine]

The “poetry of design” and “engineering energized by poetry,” eh? (I have a few comments about science, in my September 11, 2023 posting; scroll down to the ‘Poetry and physics’ subhead.)

Back on topic, here’s a link to and a citation for the paper,

Multiscale design of cell-free biologically active architectural structures by G. Ho, V. Kubušová, C. Irabien, V. Li, A. Weinstein, Sh. Chawla, D. Yeung, A. Mershin, K. Zolotovsky, L. Mogas-Soldevila. Front. Bioeng. Biotechnol., 28 March 2023 Volume 11 – 2023 DOI: https://doi.org/10.3389/fbioe.2023.1125156

This paper appears to be open access.

Fluid mechanics in the kitchen

Caption: Dr. Maciej Lisicki is developing a formula for perfectly creamy ice cream in his laboratory. Credit Photo: Michal Czerepaniak, source: Faculty of Physics, University of Warsaw.

It’s unusual to see a scientist in an orange (maybe it could be called fire engine red?) jumpsuit as it has an altogether different meaning (prison wear) in the US.

Sadly, there isn’t a video of Dr. Maciej Lisicki or other scientists in the kitchen but here’s a description of what they’ve been up to from a June 22, 2023 University of Warsaw (Poland) press release (also on EurekAlert),

Take four brilliant physicists who specialize in fluid mechanics and put them in the kitchen. Give them pots, pans, basic foodstuffs, and a bottle of champagne. Add a COVID-19 pandemic, a pinch of boredom, and a handful of good ideas. Stir, wait, and voilà – you have a “delicious” publication that will teach you how bubbles are created in champagne, how to brew the perfect espresso, and how “kitchen revolutions” can contribute to innovations in many fields, including biomedicine and nanotechnology.

Most of us visit this place every day. But the kitchen is not just for cooking meals. “It can be an excellent place to conduct experiments and even make scientific discoveries,” argues Maciej Lisicki, of the Faculty of Physics of the University of Warsaw, co-author of a publication in the prestigious journal Reviews of Modern Physics. The team of researchers, which in addition to Maciej Lisicki includes Arnold Mathijssen of the University of Pennsylvania, Endre J.L. Mossige of the University of Oslo and Vivek N. Prakash of the University of Miami, not only explores the history of food science, but also shows how phenomena in the kitchen lead to innovations in biomedicine and nanotechnology.

COVID pandemic and bubbles in champagne

Maciej Lisicki and his fellow researchers began working on the article during the COVID-19 pandemic, when many researchers could not work in the lab and began experimenting in their homes. “It started primarily with the intention to make an educational tool, given that kitchens offer a low barrier of entry to doing science — all you need are some pots, pans, and a few ingredients to get a few reactions going—but it quickly grew into a more scientific reflection of the history of food once we realized how interwoven the fields are,” says Arnold Mathijssen.

The team of researchers constructed the results of their work along the lines of a menu. “Tasting” begins with the physics of drinks and cocktails, then moves on to main courses, and finishes with coffee and desserts, whose preparation is also based on the intuitive use of the laws of nature.

As with any good party, everything begins with the opening of a bottle of champagne. After a characteristic “pop”, we observe how a mist forms around the neck of the bottle. – This phenomenon is associated with a rapid change in pressure. Inside the bottle it reaches almost five atmospheres, but when the bottle is opened it drops to one atmosphere.  “The expansion is accompanied by a drop in temperature, which causes the water vapor that accumulates near the mouth of the bottle to freeze, and the carbon dioxide coming out of the bottle to condense”, Maciej Lisicki explains.

In their paper, the researchers also look at bubbles, which give sparkling wines their unique flavor. “Circulating bubbles force the transport of the liquid in the glass, and thus facilitate the release and spread of aromatic notes and flavors”, the researcher adds. From the section of the paper devoted to drinks and cocktails, we will also learn what makes the foam in beer so thick and stable, why aniseed drinks such as rakija and ouzo get cloudy when enough water is added (the phenomenon is even called the “ouzo effect”), and what “tears of wine” are.

When water surfs the pan

Moving on to the main course, the scientists explain the role of heat and its effect on food textures, aromas, and flavors. Among other things, they describe the Leidenfrost effect, in which a drop of liquid placed on a very hot surface forms an insulating layer of vapor, that prevents rapid boiling. “Water drops thrown onto the pan ‘surf’ and even bounce off the surface, instead of evaporating immediately”, Lisicki says. 

Proper temperature is crucial in the preparation of many foods. “It doesn’t take a Ph.D. in physics to fry the perfect steak. Everyone knows that one needs to quickly sear the meat in a sufficiently hot pan. As a result, the proteins on the surface of the steak coagulate and the moisture is kept inside”, the researcher explains. 

A Ph.D. in dishwashing

The text also includes examples of scientific discoveries that researchers have made without leaving their own kitchens. One of them is related to the biography of Agnes Pockels.

“Her story speaks of the inequality in science. She was a woman in Germany in the late 19th century, so she was not allowed to attend university for formal training, making it difficult for her to submit her research to journals,” Mathijssen says.

Running her parents’ household and spending a lot of time in the kitchen, she quickly began experimenting there. “Observing the formation of foam and films on the surface of dirty dishes, she was the first to describe the phenomenon of surface tension and developed an instrument to measure it. Initially, scientific journals were reluctant to publish the results of her experiments due to her lack of formal training and affiliation with university staff. Her first paper was published through Lord Rayleigh in Nature and contributed to the understanding of surface effects in liquids. Agnes Pockels then became well-known and respected, and all her subsequent work was published in high-profile journals. This example shows that it is possible to become a respected scientist without leaving home,” notes Maciej Lisicki.

Salad dressing vs. nanoengineering

Research in fluid mechanics can help improve food processing technologies, as well as find applications in other fields such as nanoengineering and medicine. “In an earlier study (“Rechargeable self-assembled droplet microswimmers driven by surface phase transitions”, published in Nature Physics) conducted by my team, we used a simple emulsion that is the basis of salad dressings – oil with water. We were able to make droplets of such an emulsion, with the addition of a surfactant, form tendrils under temperature and move like bacteria. Such nontoxic, biocompatible microfluidics could be used in the future, for example, to precisely deliver drugs anywhere in our bodies”, Lisicki explains. 

The review also highlights the applicability of these technologies in areas such as food safety and quality control. By deploying devices that can detect food-borne pathogens or toxins using principles of fluid dynamics, the scientific community can contribute significantly to public health.

Another key aspect of their review is the potential impact it could have on policy decisions, particularly those related to environmental sustainability and food safety. The authors highlight the significance of science-based policies, for example – referencing the announced EU ban on PFAS non-stick coatings by 2030. Using the scientific understanding offered by studies like these, policy makers can make informed decisions to foster a more sustainable and safer food future.

“Kitchen flows show us that significant scientific problems are available at our fingertips and do not always require space technology to explore them. On the other hand, more than a few cosmic technologies were born from inspiration by everyday phenomena. The kitchen can therefore entertain us, but also teach us – in this case, physics. This is why it is worth a try to unleash your curiosity and experiment!” Lisicki adds.

This research was supported by the United States Department of Agriculture (USDA-NIFA AFRI 2020-67017-30776 and 2020-67015-32330).

Faculty of Physics of the University of Warsaw
Physics and astronomy at the University of Warsaw appeared in 1816 as part of the then Faculty of Philosophy. In 1825, the Astronomical Observatory was established. Currently, the Faculty of Physics at the University of Warsaw consists of the following institutes: Experimental Physics, Theoretical Physics, Geophysics, the Department of Mathematical Methods and the Astronomical Observatory. The research covers almost all areas of modern physics, on scales from quantum to cosmological. The Faculty’s research and teaching staff consists of over 200 academic teachers, 88 of whom are professors. About 1,100 students and over 170 doctoral students study at the Faculty of Physics at the University of Warsaw.

Perhaps the paper provides more information about the ice cream research depicted in the visual image at the top of this posting. Here’s a link to and a citation for the paper,

Culinary fluid mechanics and other currents in food science by Arnold J. T. M. Mathijssen, Maciej Lisicki, Vivek N. Prakash, and Endre J. L. Mossige. Rev. Mod. Phys. Vol. 95, Iss. 2 — April – June 2023 025004 DOI: https://doi.org/10.1103/RevModPhys.95.025004 Published: 5 June 2023 © 2023 American Physical Society

This paper is behind a paywall.

Smart dental implant resists bacterial growth and generates own electricity

A “smart” dental implant could improve upon current devices by employing biofilm-resisting nanoparticles and a light powered by biomechanical forces to promote health of the surrounding gum tissue. (Image: Courtesy of Albert Kim)

A September 9, 2021 news item on ScienceDaily announces research into ‘smart’ dental implants,

More than 3 million people in America have dental implants, used to replace a tooth lost to decay, gum disease, or injury. Implants represent a leap of progress over dentures or bridges, fitting much more securely and designed to last 20 years or more.

But often implants fall short of that expectation, instead needing replacement in five to 10 years due to local inflammation or gum disease, necessitating a repeat of a costly and invasive procedure for patients.

“We wanted to address this issue, and so we came up with an innovative new implant,” says Geelsu Hwang, an assistant professor in the University of Pennsylvania School of Dental Medicine, who has a background in engineering that he brings to his research on oral health issues.

The novel implant would implement two key technologies, Hwang says. One is a nanoparticle-infused material that resists bacterial colonization. And the second is an embedded light source to conduct phototherapy, powered by the natural motions of the mouth, such as chewing or toothbrushing. In a paper in the journal ACS Applied Materials & Interfaces and a 2020 paper in the journal Advanced Healthcare Materials, Hwang and colleagues lay out their platform, which could one day be integrated not only into dental implants but other technologies, such as joint replacements, as well.

A September 9, 2021 University of Pennsylvania news release (also on EurekAlert), which originated the news item, provides more technical details about the proposed technology,

“Phototherapy can address a diverse set of health issues,” says Hwang. “But once a biomaterial is implanted, it’s not practical to replace or recharge a battery. We are using a piezoelectric material, which can generate electrical power from natural oral motions to supply a light that can conduct phototherapy, and we find that it can successfully protect gingival tissue from bacterial challenge.”

In the paper, the material the researchers explored was barium titanate (BTO), which has piezoelectric properties that are leveraged in applications such as capacitators and transistors, but has not yet been explored as a foundation for anti-infectious implantable biomaterials. To test its potential as the foundation for a dental implant, the team first used discs embedded with nanoparticles of BTO and exposed them to Streptococcus mutans, a primary component of the bacterial biofilm responsible for tooth decay commonly known as dental plaque. They found that the discs resisted biofilm formation in a dose-dependent manner. Discs with higher concentrations of BTO were better at preventing biofilms from binding.

While earlier studies had suggested that BTO might kill bacteria outright using reactive oxygen species generated by light-catalyzed or electric polarization reactions, Hwang and colleagues did not find this to be the case due to the short-lived efficacy and off-target effects of these approaches. Instead, the material generates enhanced negative surface charge that repels the negatively charged cell walls of bacteria. It’s likely that this repulsion effect would be long-lasting, the researchers say.

“We wanted an implant material that could resist bacterial growth for a long time because bacterial challenges are not a one-time threat,” Hwang says.

The power-generating property of the material was sustained and in tests over time the material did not leach. It also demonstrated a level of mechanical strength comparable to other materials used in dental applications.

Finally, the material did not harm normal gingival tissue in the researchers’ experiments, supporting the idea that this could be used without ill effect in the mouth.

The technology is a finalist in the Science Center’s research accelerator program, the QED Proof-of-Concept program. As one of 12 finalists, Hwang and colleagues will receive guidance from experts in commercialization. If the project advances to be one of three finalists, the group has the potential to receive up to $200,000 in funding.

In future work, the team hopes to continue to refine the “smart” dental implant system, testing new material types and perhaps even using assymetric properties on each side of the implant components, one that encourages tissue integration on the side facing the gums and one that resists bacterial formation on the side facing the rest of the mouth.

“We hope to further develop the implant system and eventually see it commercialized so it can be used in the dental field,” Hwang says.

Here’s a link to and a citation for the paper,

Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications by Atul Dhall, Sayemul Islam, Moonchul Park, Yu Zhang, Albert Kim, and Geelsu Hwang. ACS Appl. Mater. Interfaces 2021, 13, 34, 40379–40391 DOI: https://doi.org/10.1021/acsami.1c11791 Publication Date:August 18, 2021 Copyright © 2021 American Chemical Society

This paper is behind a paywall.

The work from 2020, mentioned in the news release, laid groundwork for the latest paper.

Human Oral Motion-Powered Smart Dental Implant (SDI) for In Situ Ambulatory Photo-biomodulation Therapy by Moonchul Park, Sayemul Islam, Hye-Eun Kim, Jonathan Korosto, Markus B. Blatz, Geelsu Hwang, and Albert Kim. Adv. Healthcare Mater. 2020, 9, 2000658 DOI: 10.1002/adhm.202000658 First published: 01 July 2020 © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimHuman

This paper is behind a paywall.

mRNA, COVID-19 vaccines, treating genetic diseases before birth, and the scientist who started it all

This post was going to be about new research into fetal therapeutics and mRNA.But, since I’ve been very intrigued by the therapeutic agent, mRNA, which has been a big part of the COVID-19 vaccine story; this seemed like a good opportunity to dive a little more deeply into that topic at the same time.

It’s called messenger ribonucleic acid (mRNA) and until seeing this video I had only the foggiest idea of how it works, which is troubling since at least two COVID-19 vaccines are based on this ‘new’ technology. From a November 10, 2020 article by Damian Garde for STAT,

Garde’s article offers detail about mRNA along with fascinating insight into how science and entreneurship works.

mRNA—it’s in the details, plus, the loneliness of pioneer researchers, a demotion, and squabbles

Garde’s November 10, 2020 article provides some explanation about how mRNA vaccines work and it takes a look at what can happen to pioneering scientists (Note: A link has been removed),

For decades, scientists have dreamed about the seemingly endless possibilities of custom-made messenger RNA, or mRNA.

Researchers understood its role as a recipe book for the body’s trillions of cells, but their efforts to expand the menu have come in fits and starts. The concept: By making precise tweaks to synthetic mRNA and injecting people with it, any cell in the body could be transformed into an on-demand drug factory. [emphasis mine]

But turning scientific promise into medical reality has been more difficult than many assumed. Although relatively easy and quick to produce compared to traditional vaccine-making, no mRNA vaccine or drug has ever won approval [until 2021].

Whether mRNA vaccines succeed or not, their path from a gleam in a scientist’s eye to the brink of government approval has been a tale of personal perseverance, eureka moments in the lab, soaring expectations — and an unprecedented flow of cash into the biotech industry.

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.

It all made sense on paper. In the natural world, the body relies on millions of tiny proteins to keep itself alive and healthy, and it uses mRNA to tell cells which proteins to make. If you could design your own mRNA, you could, in theory, hijack that process and create any protein you might desire — antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.

In 1990, researchers at the University of Wisconsin managed to make it work in mice. Karikó wanted to go further.

The problem, she knew, was that synthetic RNA was notoriously vulnerable to the body’s natural defenses, meaning it would likely be destroyed before reaching its target cells. And, worse, the resulting biological havoc might stir up an immune response that could make the therapy a health risk for some patients.

It was a real obstacle, and still may be, but Karikó was convinced it was one she could work around. Few shared her confidence.

“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. 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.

“I thought of going somewhere else, or doing something else,” Karikó said. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”

In time, those better experiments came together. After a decade of trial and error, Karikó and her longtime collaborator at Penn — Drew Weissman, an immunologist with a medical degree and Ph.D. from Boston University — discovered a remedy for mRNA’s Achilles’ heel.

The stumbling block, as Karikó’s many grant rejections pointed out, was that injecting synthetic mRNA typically led to that vexing immune response; the body sensed a chemical intruder, and went to war. The solution, Karikó and Weissman discovered, was the biological equivalent of swapping out a tire.

Every strand of mRNA is made up of four molecular building blocks called nucleosides. But in its altered, synthetic form, one of those building blocks, like a misaligned wheel on a car, was throwing everything off by signaling the immune system. So Karikó and Weissman simply subbed it out for a slightly tweaked version, creating a hybrid mRNA that could sneak its way into cells without alerting the body’s defenses.

“That was a key discovery,” said Norbert Pardi, an assistant professor of medicine at Penn and frequent collaborator. “Karikó and Weissman figured out that if you incorporate modified nucleosides into mRNA, you can kill two birds with one stone.”

That discovery, described in a series of scientific papers starting in 2005, largely flew under the radar at first, said Weissman, but it offered absolution to the mRNA researchers who had kept the faith during the technology’s lean years. And it was the starter pistol for the vaccine sprint to come.

Entrepreneurs rush in

Garde’s November 10, 2020 article shifts focus from Karikó, Weissman, and specifics about mRNA to the beginnings of what might be called an entrepreneurial gold rush although it starts sedately,

Derrick Rossi [emphasis mine], a native of Toronto who rooted for the Maple Leafs and sported a soul patch, was a 39-year-old postdoctoral fellow in stem cell biology at Stanford University in 2005 when he read the first paper. Not only did he recognize it as groundbreaking, he now says Karikó and Weissman deserve the Nobel Prize in chemistry.

“If anyone asks me whom to vote for some day down the line, I would put them front and center,” he said. “That fundamental discovery is going to go into medicines that help the world.”

But Rossi didn’t have vaccines on his mind when he set out to build on their findings in 2007 as a new assistant professor at Harvard Medical School running his own lab.

He wondered whether modified messenger RNA might hold the key to obtaining something else researchers desperately wanted: a new source of embryonic stem cells [emphasis mine].

In a feat of biological alchemy, embryonic stem cells can turn into any type of cell in the body. That gives them the potential to treat a dizzying array of conditions, from Parkinson’s disease to spinal cord injuries.

But using those cells for research had created an ethical firestorm because they are harvested from discarded embryos.

Rossi thought he might be able to sidestep the controversy. He would use modified messenger molecules to reprogram adult cells so that they acted like embryonic stem cells.

He asked a postdoctoral fellow in his lab to explore the idea. In 2009, after more than a year of work, the postdoc waved Rossi over to a microscope. Rossi peered through the lens and saw something extraordinary: a plate full of the very cells he had hoped to create.

Rossi excitedly informed his colleague Timothy Springer, another professor at Harvard Medical School and a biotech entrepreneur. Recognizing the commercial potential, Springer contacted Robert Langer, the prolific inventor and biomedical engineering professor at the Massachusetts Institute of Technology.

On a May afternoon in 2010, Rossi and Springer visited Langer at his laboratory in Cambridge. What happened at the two-hour meeting and in the days that followed has become the stuff of legend — and an ego-bruising squabble.

Langer is a towering figure in biotechnology and an expert on drug-delivery technology. At least 400 drug and medical device companies have licensed his patents. His office walls display many of his 250 major awards, including the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers.

As he listened to Rossi describe his use of modified mRNA, Langer recalled, he realized the young professor had discovered something far bigger than a novel way to create stem cells. Cloaking mRNA so it could slip into cells to produce proteins had a staggering number of applications, Langer thought, and might even save millions of lives.

“I think you can do a lot better than that,” Langer recalled telling Rossi, referring to stem cells. “I think you could make new drugs, new vaccines — everything.”

Within several months, Rossi, Langer, Afeyan [Noubar Afeyan, venture capitalist, founded and runs Flagship Ventures], and another physician-researcher at Harvard formed the firm Moderna — a new word combining modified and RNA.

Springer was the first investor to pledge money, Rossi said. In a 2012 Moderna news release, Afeyan said the firm’s “promise rivals that of the earliest biotechnology companies over 30 years ago — adding an entirely new drug category to the pharmaceutical arsenal.”

But although Moderna has made each of the founders hundreds of millions of dollars — even before the company had produced a single product — Rossi’s account is marked by bitterness. In interviews with the [Boston] Globe in October [2020], he accused Langer and Afeyan of propagating a condescending myth that he didn’t understand his discovery’s full potential until they pointed it out to him.

Garde goes on to explain how BioNTech came into the mRNA picture and contrasts the two companies’ approaches to biotechnology as a business. It seems BioNTech has not cashed in the same way as has Moderna. (For some insight into who’s making money from COVID-19 check out Giacomo Tognini’s December 23, 2020 article (Meet The 50 Doctors, Scientists And Healthcare Entrepreneurs Who Became Pandemic Billionaires In 2020) for Forbes.)

Garde ends his November 10, 2020 article on a mildly cautionary note,

“You have all these odd clinical and pathological changes caused by this novel bat coronavirus [emphasis mine], and you’re about to meet it with all of these vaccines with which you have no experience,” said Paul Offit, an infectious disease expert at Children’s Hospital of Philadelphia and an authority on vaccines.

What happened to Katalin Karikó?

Matthew Rosza’s January 25, 2021 article about Karikó and her pioneering work features an answer to my question and some advice,

“I want young people to feel — if my example, because I was demoted, rejected, terminated, I was even subject for deportation one point — [that] if they just pursue their thing, my example helps them to wear rejection as a badge,” Karikó, who today is a senior vice president at BioNTech RNA Pharmaceuticals, told Salon last month when discussing her story. “‘Okay, well, I was rejected. I know. Katalin was rejected and still [succeeded] at the end.’ So if it helps them, then it helps them.”

Despite her demotion, Karikó continued with her work and, along with a fellow immunologist named Dr. Drew Weissman, penned a series of influential articles starting in 2005. These articles argued that mRNA vaccines would not be neutralized by the human immune system as long as there were specific modifications to nucleosides, a compound commonly found in RNA.

By 2013, Karikó’s work had sufficiently impressed experts that she left the University of Pennsylvania for BioNTech RNA Pharmaceuticals.

Karikó tells Salon that the experience taught her one important lesson: In life there will be people who, for various reasons, will try to hold you back, and you can’t let them get you down.

“People that are in power, they can help you or block you,” Karikó told Salon. “And sometimes people select to make your life miserable. And now they cannot be happy with me because now they know that, ‘Oh, you know, we had the confrontation and…’ But I don’t spend too much time on these things.”

Before moving onto the genetic research which prompted this posting, I have an answer to the following questions:

Could an mRNA vaccine affect your DNA (deoxyribonucleic acid) and how do mRNA vaccines differ from the traditional ones?

No, DNA is not affected by the COVID-19 mRNA vaccines, according to a January 5, 2021 article by Jason Murdock for Newsweek,

The type of vaccines used against COVID-19 do not interact with or alter human genetic code, also known as DNA, scientists say.

In traditional vaccines, a piece of a virus, known as an “antigen,” would be injected into the body to force the immune system to make antibodies to fight off future infection. But mRNA-based methods do not use a live virus, and cannot give someone COVID.

Instead, mRNA vaccines give cells the instructions to make a “spike” protein also found on the surface of the virus that causes COVID. The body kickstarts its immune response by creating the antibodies needed to combat those specific virus proteins.

Once the spike protein is created, the cell breaks down the instructions provided by the mRNA molecule, leaving the human immune system prepared to combat infection. The mRNA vaccines are not a medicine—nor a cure—but a preventative measure.

Gavi, a vaccine alliance partnered with the World Health Organization (WHO), has said that mRNA instructions will become degraded in approximately 72 hours.

It says mRNA strands are “chemical intermediaries” between DNA in our chromosomes and the “cellular machinery that produces the proteins we need to function.”

But crucially, while mRNA vaccines will give the human body the blueprints on how to assemble proteins, the alliance said in a fact-sheet last month that “mRNA isn’t the same as DNA, and it can’t combine with our DNA to change our genetic code.”

It explained: “Some viruses like HIV can integrate their genetic material into the DNA of their hosts, but this isn’t true of all viruses… mRNA vaccines don’t carry these enzymes, so there is no risk of the genetic material they contain altering our DNA.”

The [US] Centers for Disease Control and Prevention (CDC) says on its website that mRNA vaccines that are rolling out don’t “interact with our DNA in any way,” and “mRNA never enters the nucleus of the cell, which is where our DNA (genetic material) is kept.”

Therapeutic fetal mRNA treatment

Rossi’s work on mRNA and embryonic stem cells bears a relationship of sorts to this work focusing on prebirth therapeutics. (From a January 13, 2021 news item on Nanowerk), Note: A link has been removed,

Researchers at Children’s Hospital of Philadelphia and the School of Engineering and Applied Science at the University of Pennsylvania have identified ionizable lipid nanoparticles that could be used to deliver mRNA as part of fetal therapy.

The proof-of-concept study, published in Science Advances (“Ionizable Lipid Nanoparticles for In Utero mRNA Delivery”), engineered and screened a number of lipid nanoparticle formulations for targeting mouse fetal organs and has laid the groundwork for testing potential therapies to treat genetic diseases before birth.

A January 13, 2021 Children’s Hospital of Philadelphia (CHOP) news release (also on EurekAlert), which originated the news item, delves further into the research,

“This is an important first step in identifying nonviral mediated approaches for delivering cutting-edge therapies before birth,” said co-senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at CHOP. “These lipid nanoparticles may provide a platform for in utero mRNA delivery, which would be used in therapies like fetal protein replacement and gene editing.”

Recent advances in DNA sequencing technology and prenatal diagnostics have made it possible to diagnose many genetic diseases before birth. Some of these diseases are treated by protein or enzyme replacement therapies after birth, but by then, some of the damaging effects of the disease have taken hold. Thus, applying therapies while the patient is still in the womb has the potential to be more effective for some conditions. The small fetal size allows for maximal therapeutic dosing, and the immature fetal immune system may be more tolerant of replacement therapy.

Of the potential vehicles for introducing therapeutic protein replacement, mRNA is distinct from other nucleic acids, such as DNA, because it does not need to enter the nucleus and can use the body’s own machinery to produce the desired proteins. Currently, the common methods of nucleic acid delivery include viral vectors and nonviral approaches. Although viral vectors may be well-suited to gene therapy, they come with the potential risk of unwanted integration of the transgene or parts of the viral vector in the recipient genome. Thus, there is an important need to develop safe and effective nonviral nucleic acid delivery technologies to treat prenatal diseases.

In order to identify potential nonviral delivery systems for therapeutic mRNA, the researchers engineered a library of lipid nanoparticles, small particles less than 100 nanometers in size that effectively enter cells in mouse fetal recipients. Each lipid nanoparticle formulation was used to encapsulate mRNA, which was administered to mouse fetuses. The researchers found that several of the lipid nanoparticles enabled functional mRNA delivery to fetal livers and that some of those lipid nanoparticles also delivered mRNA to the fetal lungs and intestines. They also assessed the lipid nanoparticles for toxicity and found them to be as safe or safer than existing formulations.

Having identified the lipid nanoparticles that were able to accumulate within fetal livers, lungs, and intestines with the highest efficiency and safety, the researchers also tested therapeutic potential of those designs by using them to deliver erythropoietin (EPO) mRNA, as the EPO protein is easily trackable. They found that EPO mRNA delivery to liver cells in mouse fetuses resulted in elevated levels of EPO protein in the fetal circulation, providing a model for protein replacement therapy via the liver using these lipid nanoparticles.

“A central challenge in the field of gene therapy is the delivery of nucleic acids to target cells and tissues, without causing side effects in healthy tissue. This is difficult to achieve in adult animals and humans, which have been studied extensively. Much less is known in terms of what is required to achieve in utero nucleic acid delivery,” said Mitchell. “We are very excited by the initial results of our lipid nanoparticle technology to deliver mRNA in utero in safe and effective manner, which could open new avenues for lipid nanoparticles and mRNA therapeutics to treat diseases before birth.”

Here’s a link to and a citation for the paper,

Ionizable lipid nanoparticles for in utero mRNA delivery by Rachel S. Riley, Meghana V. Kashyap, Margaret M. Billingsley, Brandon White, Mohamad-Gabriel Alameh, Sourav K. Bose, Philip W. Zoltick, Hiaying Li, Rui Zhang, Andrew Y. Cheng, Drew Weissman, William H. Peranteau, Michael J. Mitchell. Science Advances 13 Jan 2021: Vol. 7, no. 3, eaba1028 DOI: 10.1126/sciadv.aba1028

This paper appears to be open access. BTW, I noticed Drew Weissman’s name as one of the paper’s authors and remembered him as one of the first to recognize Karikó’s pioneering work. I imagine that when he co-authored papers with Karikó he was risking his reputation.

Funny how a despised field of research has sparked a ‘gold rush’ for research and for riches, yes?.

“The earth is mostly made of cubes,” said Plato in 5th Century BCE. Turns out, he was right!

Theories from mathematics, physics, and geology have been used to demonstrate that the earth’s basic shape is, roughly speaking, a cube. From a July 20, 2020 news item on ScienceDaily,

Plato, the Greek philosopher who lived in the 5th century B.C.E. [before the common era], believed that the universe was made of five types of matter: earth, air, fire, water, and cosmos. Each was described with a particular geometry, a platonic shape. For earth, that shape was the cube.

Science has steadily moved beyond Plato’s conjectures, looking instead to the atom as the building block of the universe. Yet Plato seems to have been onto something, researchers have found.

In a new paper in the Proceedings of the National Academy of Sciences [PNAS], a team from the University of Pennsylvania, Budapest University of Technology and Economics, and University of Debrecen [Hungary] uses math, geology, and physics to demonstrate that the average shape of rocks on Earth is a cube.

A July 17, 2020 University of Pennsylvania news release (also on EurekAlert but dated July 20, 2020), which originated the news item, goes on to describe the work as “mind-blowing,”

“Plato is widely recognized as the first person to develop the concept of an atom [Maybe not, scroll down to find the subhead “Leucippus and Democritus”], the idea that matter is composed of some indivisible component at the smallest scale,” says Douglas Jerolmack, a geophysicist in Penn’s School of Arts & Sciences’ Department of Earth and Environmental Science and the School of Engineering and Applied Science’s Department of Mechanical Engineering and Applied Mechanics. “But that understanding was only conceptual; nothing about our modern understanding of atoms derives from what Plato told us.

“The interesting thing here is that what we find with rock, or earth, is that there is more than a conceptual lineage back to Plato. It turns out that Plato’s conception about the element earth being made up of cubes is, literally, the statistical average model for real earth. And that is just mind-blowing.”

The group’s finding began with geometric models developed by mathematician Gábor Domokos of the Budapest University of Technology and Economics, whose work predicted that natural rocks would fragment into cubic shapes.

“This paper is the result of three years of serious thinking and work, but it comes back to one core idea,” says Domokos. “If you take a three-dimensional polyhedral shape, slice it randomly into two fragments and then slice these fragments again and again, you get a vast number of different polyhedral shapes. But in an average sense, the resulting shape of the fragments is a cube.”

Domokos pulled two Hungarian theoretical physicists into the loop: Ferenc Kun, an expert on fragmentation, and János Török, an expert on statistical and computational models. After discussing the potential of the discovery, Jerolmack says, the Hungarian researchers took their finding to Jerolmack to work together on the geophysical questions; in other words, “How does nature let this happen?”

“When we took this to Doug, he said, ‘This is either a mistake, or this is big,'” Domokos recalls. “We worked backward to understand the physics that results in these shapes.”

Fundamentally, the question they answered is what shapes are created when rocks break into pieces. Remarkably, they found that the core mathematical conjecture unites geological processes not only on Earth but around the solar system as well.

“Fragmentation is this ubiquitous process that is grinding down planetary materials,” Jerolmack says. “The solar system is littered with ice and rocks that are ceaselessly smashing apart. This work gives us a signature of that process that we’ve never seen before.”

Part of this understanding is that the components that break out of a formerly solid object must fit together without any gaps, like a dropped dish on the verge of breaking. As it turns out, the only one of the so-called platonic forms–polyhedra with sides of equal length–that fit together without gaps are cubes.

“One thing we’ve speculated in our group is that, quite possibly Plato looked at a rock outcrop and after processing or analyzing the image subconsciously in his mind, he conjectured that the average shape is something like a cube,” Jerolmack says.

“Plato was very sensitive to geometry,” Domokos adds. According to lore, the phrase “Let no one ignorant of geometry enter” was engraved at the door to Plato’s Academy. “His intuitions, backed by his broad thinking about science, may have led him to this idea about cubes,” says Domokos.

To test whether their mathematical models held true in nature, the team measured a wide variety of rocks, hundreds that they collected and thousands more from previously collected datasets. No matter whether the rocks had naturally weathered from a large outcropping or been dynamited out by humans, the team found a good fit to the cubic average.

However, special rock formations exist that appear to break the cubic “rule.” The Giant’s Causeway in Northern Ireland, with its soaring vertical columns, is one example, formed by the unusual process of cooling basalt. These formations, though rare, are still encompassed by the team’s mathematical conception of fragmentation; they are just explained by out-of-the-ordinary processes at work.

“The world is a messy place,” says Jerolmack. “Nine times out of 10, if a rock gets pulled apart or squeezed or sheared–and usually these forces are happening together–you end up with fragments which are, on average, cubic shapes. It’s only if you have a very special stress condition that you get something else. The earth just doesn’t do this often.”

The researchers also explored fragmentation in two dimensions, or on thin surfaces that function as two-dimensional shapes, with a depth that is significantly smaller than the width and length. There, the fracture patterns are different, though the central concept of splitting polygons and arriving at predictable average shapes still holds.

“It turns out in two dimensions you’re about equally likely to get either a rectangle or a hexagon in nature,” Jerolmack says. “They’re not true hexagons, but they’re the statistical equivalent in a geometric sense. You can think of it like paint cracking; a force is acting to pull the paint apart equally from different sides, creating a hexagonal shape when it cracks.”

In nature, examples of these two-dimensional fracture patterns can be found in ice sheets, drying mud, or even the earth’s crust, the depth of which is far outstripped by its lateral extent, allowing it to function as a de facto two-dimensional material. It was previously known that the earth’s crust fractured in this way, but the group’s observations support the idea that the fragmentation pattern results from plate tectonics.

Identifying these patterns in rock may help in predicting phenomenon such as rock fall hazards or the likelihood and location of fluid flows, such as oil or water, in rocks.

For the researchers, finding what appears to be a fundamental rule of nature emerging from millennia-old insights has been an intense but satisfying experience.

“There are a lot of sand grains, pebbles, and asteroids out there, and all of them evolve by chipping in a universal manner,” says Domokos, who is also co-inventor of the Gömböc, the first known convex shape with the minimal number–just two–of static balance points. Chipping by collisions gradually eliminates balance points, but shapes stop short of becoming a Gömböc; the latter appears as an unattainable end point of this natural process.

The current result shows that the starting point may be a similarly iconic geometric shape: the cube with its 26 balance points. “The fact that pure geometry provides these brackets for a ubiquitous natural process, gives me happiness,” he says.

“When you pick up a rock in nature, it’s not a perfect cube, but each one is a kind of statistical shadow of a cube,” adds Jerolmack. “It calls to mind Plato’s allegory of the cave. He posited an idealized form that was essential for understanding the universe, but all we see are distorted shadows of that perfect form.”

The human capacity for imagination, in this case linking ideas about geometry and mathematics from the 5th Century BCE to modern physics and geology and to the solar system, astounds and astonishes me. As for Jerolmack’s comment that Plato (428/427 or 424/423 – 348/347 BC) was the first to develop the concept of an atom, not everyone agrees.

Leucippus and Democritus

It may not ever be possible to determine who was the first to theorize/philosophize about atoms but there is relatively general agreement that Leucippus (5th cent.BCE) and his successor, Democritus (c. 460 – c. 370 BC) were among the first. Here’s more about Ancient Atomism and its origins from the Stanford Encyclopedia of Philosphy,

Leucippus (5th c. BCE) is the earliest figure whose commitment to atomism is well attested. He is usually credited with inventing atomism. According to a passing remark by the geographer Strabo, Posidonius (1st c. BCE Stoic philosopher) reported that ancient Greek atomism can be traced back to a figure known as Moschus or Mochus of Sidon, who lived at the time of the Trojan wars. This report was given credence in the seventeenth century: the Cambridge Platonist Henry More traced the origins of ancient atomism back, via Pythagoras and Moschus, to Moses. This theologically motivated view does not seem to claim much historical evidence, however.

Leucippus and Democritus are widely regarded as the first atomists [emphasis mine] in the Greek tradition. Little is known about Leucippus, while the ideas of his student Democritus—who is said to have taken over and systematized his teacher’s theory—are known from a large number of reports. These ancient atomists theorized that the two fundamental and oppositely characterized constituents of the natural world are indivisible bodies—atoms—and void. The latter is described simply as nothing, or the negation of body. Atoms are by their nature intrinsically unchangeable; they can only move about in the void and combine into different clusters. Since the atoms are separated by void, they cannot fuse, but must rather bounce off one another when they collide. Because all macroscopic objects are in fact combinations of atoms, everything in the macroscopic world is subject to change, as their constituent atoms shift or move away. Thus, while the atoms themselves persist through all time, everything in the world of our experience is transitory and subject to dissolution.

Although the Greek term atomos is most commonly associated with the philosophical system developed by Leucippus and Democritus, involving solid and impenetrable bodies, Plato’s [emphasis mine] Timaeus presents a different kind of physical theory based on indivisibles. The dialogue elaborates an account of the world wherein the four different basic kinds of matter—earth, air, fire, and water—are regular solids composed from plane figures: isoceles and scalene right-angled triangles. Because the same triangles can form into different regular solids, the theory thus explains how some of the elements can transform into one another, as was widely believed.

As you can see from the excerpt, they are guessing as to the source for atomism and thee are different kinds of atomism and Plato staked his own atomistic territory.

The paper

Here’s a link to and a citation for the paper followed by a statement of significance and the paper’s abstract,

Plato’s cube and the natural geometry of fragmentation by Gábor Domokos, Douglas J. Jerolmack, Ferenc Kun, and János Török. PNAS DOI: https://doi.org/10.1073/pnas.2001037117 First published July 17, 2020

This paper is behind a paywall.

Now for the Significance and the Abstract,

We live on and among the by-products of fragmentation, from nanoparticles to rock falls to glaciers to continents. Understanding and taming fragmentation is central to assessing natural hazards and extracting resources, and even for landing probes safely on other planetary bodies. In this study, we draw inspiration from an unlikely and ancient source: Plato, who proposed that the element Earth is made of cubes because they may be tightly packed together. We demonstrate that this idea is essentially correct: Appropriately averaged properties of most natural 3D fragments reproduce the topological cube. We use mechanical and geometric models to explain the ubiquity of Plato’s cube in fragmentation and to uniquely map distinct fragment patterns to their formative stress conditions.

Plato envisioned Earth’s building blocks as cubes, a shape rarely found in nature. The solar system is littered, however, with distorted polyhedra—shards of rock and ice produced by ubiquitous fragmentation. We apply the theory of convex mosaics to show that the average geometry of natural two-dimensional (2D) fragments, from mud cracks to Earth’s tectonic plates, has two attractors: “Platonic” quadrangles and “Voronoi” hexagons. In three dimensions (3D), the Platonic attractor is dominant: Remarkably, the average shape of natural rock fragments is cuboid. When viewed through the lens of convex mosaics, natural fragments are indeed geometric shadows of Plato’s forms. Simulations show that generic binary breakup drives all mosaics toward the Platonic attractor, explaining the ubiquity of cuboid averages. Deviations from binary fracture produce more exotic patterns that are genetically linked to the formative stress field. We compute the universal pattern generator establishing this link, for 2D and 3D fragmentation.

Fascinating, eh?