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Thursday, September 26, 2024

Late-stage functionalisation: a unique perspective from a research scientist turned patent attorney

Late-stage functionalisation – defined as “a desired chemoselective transformation on a complex molecule to provide at least one analog in sufficient quantity and purity for a given purpose without the necessity for installation of a functional group that exclusively serves the purpose to enable said transformation” [1] – has emerged as a valuable enabling tool within the arsenal of a medicinal chemist. As newer synthetic methods become developed for the generation of small molecules, so too has the chemical space that medicinal chemists will have access to.

Of course, these methods are valuable to the R&D team – but did you know that late-stage functionalisation will also likely have an impact on the IP profession? This perspective provides some insight into how late-stage functionalisation not only helps the chemists at the bench, but also the patent attorneys working in-house and within outside counsel who are very much off the bench.

The conventional approach to chemical synthesis – the “building block” route

Traditionally, the procedure for installing the required functionality in a small molecule typically involves utilising starting materials that already include such groups, or conducting one or more reactions that generate such groups – this stitching together of starting materials to generate the final product can be termed a “building block” approach.

The advent of late-stage functionalisation

The discovery and development of mild, chemoselective, site-selective and stereoselective reactions has fundamentally changed the way in which chemists think about synthetic chemistry. Reactions that were once considered fanciful decades ago are now enabled by recent advancements in transition metal catalysis, photoredox catalysis and the like.

For instance, it is now perfectly reasonable to think of various C-H groups as reactive handles at which functionality can be installed by C-H functionalisation [2].The medicinal chemist’s perspective

During the course of R&D, it is necessary to investigate structure-activity relationships (SAR). By investigating different types of substituents at various positions of a small molecule, the biological activity of the compound can be optimised.

The traditional “building block” approach can often conflict with the types of modifications desired when investigating SAR. Of course, it can be easier to investigate the effect of swapping out certain substituents if they were already introduced at a late stage of the synthetic route, illustrated schematically and with the example of imatinib below:

“wherein R1 is selected from hydrogen, halogen, OH, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group”.

We have discussed in previous articles of our Data driven IP insights series that experimental evidence will be required showing how the invention can be reproduced by others (or, in legalese, by the notional “person having ordinary skill in the art” or “skilled person”). For a patent application relating to small molecules, this is typically achieved by providing synthetic procedures and characterisation data in the patent specification for a number of chemical compounds falling within the scope of such a Markush structure, much like the supplementary information section in a journal article.

The amount of experimental data required to “support” a claim to such a general chemical structure will very much depend on where you are pursuing patent protection.

Some jurisdictions may be relatively more lenient and will allow such claims to grant, even though not all substituent types have been exemplified by the experimental data of the patent specification (e.g. if an alkyl group has been exemplified in the examples for R1 in the Markush structure above, but not alkenyl or alkynyl groups).

However, other countries can be stricter, requiring that each substituent type be exemplified by at least one compound in the patent specification (e.g. if only an alkyl group has been exemplified in the examples for R1 in the Markush structure above, then the remaining substituents listed for R1 that are not exemplified may need to be deleted, before the patent office will allow the claim to grant). In such jurisdictions, the need to limit the scope of protection of the claims may be undesirable and can make it easier for third parties to work around the protection afforded by a granted patent.

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Wednesday, September 25, 2024

Do AI models produce more original ideas than researchers?

An ideas generator powered by artificial intelligence (AI) came up with more original research ideas than did 50 scientists working independently, according to a preprint posted on arXiv this month1.

The human and AI-generated ideas were evaluated by reviewers, who were not told who or what had created each idea. The reviewers scored AI-generated concepts as more exciting than those written by humans, although the AI’s suggestions scored slightly lower on feasibility.

But scientists note that the study, which has not been peer-reviewed, has limitations. It focused on one area of research and required human participants to come up with ideas on the fly, which probably hindered their ability to produce their best concepts.
AI in science

There are burgeoning efforts to explore how LLMs can be used to automate research tasks, including writing papers, generating code and searching literature. But it’s been difficult to assess whether these AI tools can generate fresh research angles at a level similar to that of humans. That’s because evaluating ideas is highly subjective and requires gathering researchers who have the expertise to assess them carefully, says study co-author, Chenglei Si. “The best way for us to contextualise such capabilities is to have a head-to-head comparison,” says Si, a computer scientist at Stanford University in California.

The year-long project is one of the biggest efforts to assess whether large language models (LLMs) — the technology underlying tools such as ChatGPT — can produce innovative research ideas, says Tom Hope, a computer scientist at the Allen Institute for AI in Jerusalem. “More work like this needs to be done,” he says.

The team recruited more than 100 researchers in natural language processing — a branch of computer science that focuses on communication between AI and humans. Forty-nine participants were tasked with developing and writing ideas, based on one of seven topics, within ten days. As an incentive, the researchers paid the participants US$300 for each idea, with a $1,000 bonus for the five top-scoring ideas.

Meanwhile, the researchers built an idea generator using Claude 3.5, an LLM developed by Anthropic in San Francisco, California. The researchers prompted their AI tool to find papers relevant to the seven research topics using Semantic Scholar, an AI-powered literature-search engine. On the basis of these papers, the researchers then prompted their AI agent to generate 4,000 ideas on each research topic and instructed it to rank the most original ones.
Human reviewers

Next, the researchers randomly assigned the human- and AI-generated ideas to 79 reviewers, who scored each idea on its novelty, excitement, feasibility and expected effectiveness. To ensure that the ideas’ creators remained unknown to the reviewers, the researchers used another LLM to edit both types of text to standardize the writing style and tone without changing the ideas themselves.

On average, the reviewers scored the AI-generated ideas as more original and exciting than those written by human participants. However, when the team took a closer look at the 4,000 LLM-produced ideas, they found only around 200 that were truly unique, suggesting that the AI became less original as it churned out ideas.

When Si surveyed the participants, most admitted that their submitted ideas were average compared with those they had produced in the past.

The results suggest that LLMs might be able to produce ideas that are slightly more original than those in the existing literature, says Cong Lu, a machine-learning researcher at the University of British Columbia in Vancouver, Canada. But whether they can beat the most groundbreaking human ideas is an open question.

Another limitation is that the study compared written ideas that had been edited by an LLM, which altered the language and length of the submissions, says Jevin West, a computational social scientist at the University of Washington in Seattle. Such changes could have subtly influenced how reviewers perceived novelty, he says. West adds that pitting researchers against an LLM that can generate thousands of ideas in hours might not make for a totally fair comparison. “You have to compare apples to apples,” he says.

Si and his colleagues are planning to compare AI-generated ideas with leading conference papers to gain a better understanding of how LLMs stack up against human creativity. “We are trying to push the community to think harder about how the future should look when AI can take on a more active role in the research process,” he says.

Tuesday, September 24, 2024

New research instruments bring new possibilities to Binghamton

3D X-ray microscope

The Analytical and Diagnostics Laboratory added a $1.7 million Zeiss 620 Versa Xradia instrument to its suite of tools, which are available to campus researchers and industry partners. The Xradia, a 3D X-ray microscope, is capable of tremendous magnification without destroying a sample.

Senior scientist Anju Sharma says the versatile instrument is suited to a broad range of applications; it can capture images of biological materials, whole electronic devices, 3D printed parts, batteries, rocks, fossils and more. Images in 2D are collected as a sample rotates under X-ray; powerful software reconstructs them into a 3D volume that can be virtually cross-sectioned at any location or orientation.

“It can do truly nondestructive characterization and give you very high-resolution data,” Sharma says. “You can look at the micro world inside a large-scale object.”

She says a quick scan can be conducted in an hour, while other tests may take a few hours or more. The Xradia system also enables scientists to do “4D experiments,” in which a 3D microstructure is subjected to compression, extension or changes in temperature over time.

Sharma recently worked with an industry user to examine a large circuit board that had experienced an electrical failure. The Xradia made it possible to find a tiny crack in a solder joint without destroying the board.

“With other electron microscopes, you can look at the surface,” she says. “You can’t look inside.”

Posted in: Science & Technology, Watson

MRI-centered research, a cross-disciplinary pursuit, blends expertise in physics, anatomy, physiology, neuroscience and advanced data processing. A new $2.6M functional MRI scanner will advance research at Binghamton as well as clinical possibilities for United Health Services. Image Credit: Jonathan Cohen.

Three major pieces of state-of-the-art research instrumentation recently debuted at Binghamton University, each with potential to contribute to advances in fields such as engineering, materials science and human health.

Magnetic resonance imaging (MRI)

The University purchased a $2.6 million Siemens Magnetom Prisma 3 Tesla scanner as part of a collaborative venture with United Health Services, leading to the establishment of the Binghamton Brain and Body Imaging Research Center.

The center, led by Distinguished Professor J. David Jentsch, will deepen our scientific understanding of brain disorders.

“The fundamental goal of MRI is to see what should be unseeable, what’s inside the deep recesses of your body,” Jentsch says. “But that’s kind of what makes MRI remarkable. I like to think of this as being one of the few machines that the human brain created to see and to heal itself. That really sets it apart from other kinds of healthcare and research technology.”

The project was about a decade in the making, says University President Harvey Stenger, who notes that it’s novel to embed a research tool inside a working healthcare facility.

“It’s almost impossible to think about the brain being understood like we understand a bone or a muscle,” he says, “but with the new computational artificial intelligence breakthroughs, professors like David Jentsch and future faculty, I really do think that the brain will be understood at a fundamental level so that we can predict the cause of terrible diseases and disorders like autism and Parkinson’s and Alzheimer’s. That’s the goal.”

HArd X-ray Photoelectron Spectroscopy (HAXPES)

The University’s Analytical and Diagnostics Laboratory, part of the S3IP Center of Excellence, offers core facilities to the entire campus community as well as to industry partners. The lab acquired a HArd X-ray Photoelectron Spectroscopy, or HAXPES, system with support from the National Science Foundation’s Major Research Instrumentation program.

The $2 million Scienta Omicron HAXPES tool is the first of its kind in North America.

Matthew J. Wahila, chief technology officer for the center, says the lab is especially useful for scientists who want to get the “fingerprint,” or chemical composition, of a sample. For instance, the Binghamton lab has already been used by chemists to analyze cathode powders for batteries.

“It helps you understand the samples that you’re fabricating,” Wahila says. “Exact composition can be very important, especially if you’re talking about doping materials where you could be putting in a fraction of a percent of one type of atom and that can have drastic effects on the properties.”

HAXPES will enable scientists to get that kind of understanding and iterate or improve their fabrication procedures more quickly than if they had to wait for an opportunity to travel to a synchrotron to conduct an experiment.

Monday, September 23, 2024

Team Finds Positively Brighter Understanding of How Kidneys Work

Gold nanoparticles are key to University of Texas at Dallas research that has changed researchers’ understanding of how kidneys work at the fundamental level.

New research by University of Texas at Dallas scientists is providing fundamental insight into how the kidneys remove materials from the blood and excrete them into the urine based on the electric charge of the materials.

The findings, published May 28 in Proceedings of the National Academy of Sciences, could lead to improvements in nanomedicines used for early detection and treatment of kidney damage or disease, as well as disease in other areas of the body.

“Our research findings were surprising and also very significant because they change people’s understanding of how the kidney works at the fundamental level,” said Dr. Jie Zheng, professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics and a corresponding author of the study.

PhD’20, a research scientist in Zheng’s lab and the study’s lead author.

Understanding how the kidney processes substances based on charge is important because nanomedicines, which use nanoparticles to deliver imaging agents and drugs to specific parts of the body, are already in use for diagnosis and treatment of disease and injury, including cancer, Zheng said. Delivery particles eventually must be eliminated from the body, with those smaller than 8 nanometers often leaving through the urinary tract, which starts with the kidneys.

“The kidney is the clearance route to eliminate these particles from the body once they have delivered their payload,” said Dr. Mengxiao Yu, research associate professor of chemistry and biochemistry and a corresponding author of the study. “If we use them to treat other areas of the body, we want to minimize the interaction the particles have with the kidney so that they will pass easily and not damage the organ. On the other hand, treating kidney disease requires stronger nanoparticle interactions with the kidneys. Understanding how charge affects this interaction can help tailor nanoparticles to better meet these needs.”

“It was previously thought that the glomerulus was the primary charge barrier in the kidney, but our experiments provide clear evidence that that is not true.”

Dr. Jie Zheng, professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics

In the kidney, blood flows into millions of filtering units called nephrons, each of which contains a glomerulus — a cluster of tiny blood vessels — as well as tubules and capillaries. Using the nanoparticles as probes allowed the researchers to understand which component of the kidney’s complex structure is most negatively charged.

The results were unexpected.

The researchers found that the proximal tubule was the most negatively charged area and that the peritubular capillary was a secondary barrier to the transport of charged nanoparticles within the kidney. The glomerulus came in third.

“It was previously thought that the glomerulus was the primary charge barrier in the kidney, but our experiments provide clear evidence that that is not true,” Zheng said.

The researchers also determined that when positively charged nanoparticles interact with negatively charged cell membranes, the strength of that attraction is dependent primarily on the distance between the two, in addition to the charge density of each.

According to the Centers for Disease Control and Prevention, chronic kidney disease (CKD), a condition in which a person’s damaged kidneys cannot effectively filter waste from the blood, is a leading cause of death in the U.S. More than 35 million U.S. adults are estimated to have CKD, and most are undiagnosed.

The UT Dallas researchers said a better understanding of how kidney disease or damage changes the electrical charge barriers in kidney cells could inform the design of nanomedicines that target specific diseased sites and leave normal kidney cells unaffected.

“This is important because, for example, in acute kidney injury, the site of major damage is the proximal tubules,” Huang said. “But early damage induced by infectious disease often occurs first in the peritubular capillaries. Our work demonstrates that in the future, we could tune nanoparticles to different kinds of kidney disease.”

The results complement earlier research by the UT Dallas team, which previously determined how the size of nanoparticles is related to their clearance from the kidneys.

“In 2017 we figured out the size barrier. Now we finally figured out the charge barrier, which is much more complicated,” Zheng said.

The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (R01DK124881, R01DK115986); and the Cancer Prevention and Research Institute of Texas (RP200233).

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Saturday, September 21, 2024

The discovery of a new blood group, MAL, has solved a 50- year-old mystery. Researchers from NHS Blood and Transplant (Bristol), NHSBT’s International Blood Group Reference Laboratory (IBGRL) and the University of Bristol identified the genetic background of the previously known but mysterious AnWj blood group antigen. The findings allow identification and treatment of rare patients lacking this blood group.

Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals – though due to this discovery it will now be easier to find others in the future.

The two best known blood group systems are ABO and Rh but blood is more complex and matching across the other groups can be lifesaving.

If people who are AnWj-negative receive AnWj-positive blood they could have a transfusion reaction, and this research allows development of new genotyping tests for detecting such rare individuals and reducing the risk of transfusion-associated complications.

The AnWj antigen – an antigen is a surface marker - was discovered in 1972 but its genetic background was unknown until now.(3) The new research, to be published by Blood, the journal of the American Society of Hematology, and now available online in pre-print, establishes a new blood group system (MAL), the 47th ever to be discovered, as home to the AnWj antigen.

The research team established that AnWj is carried on the Mal protein. More than 99.9% of people are AnWj-positive, and such individuals were shown to express full-length Mal protein on their red cells, which was not present on the cells of AnWj-negative individuals. The team identified homozygous deletions in the MAL gene associated with the inherited AnWj-negative phenotype.

The most common reason for being AnWj-negative is due to suffering from a haematological disorder or some types of cancer which suppress antigen expression (4). Only a very small number of people are AnWj-negative due to a genetic cause. There were five genetically AnWj negative individuals in the study including a family of Arab-Israelis.(5) The blood tested included a sample given by a lady in 2015 who was the first AnWj negative person to be discovered in the 1970s.

The research team used whole exome sequencing – the genetic sequencing of all DNA that encodes proteins – to show that these rare inherited cases were caused by homozygous DNA sequence deletions in the MAL gene, which codes for Mal protein.

Proof that Mal is responsible for binding of AnWj antibodies isolated from these rare patients was provided by experiments showing the appearance of specific reactivity with cells in which researchers introduced the normal MAL gene but not the mutant gene.

Louise Tilley, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, said: “The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career. It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients.

“The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells. Proving our findings was challenging, and we appreciate the help of all our collaborators, and the patients, without whom we would not have got to this point.”

Ash Toye, Professor of Cell Biology in the School of Biochemistry and Director of the NIHR Blood and Transplant Research Unit in red cell products at the University of Bristol, said: “It’s really exciting we were able use our ability to manipulate gene expression in the developing blood cells to help confirm the identity of the AnWj blood group, which has been an outstanding puzzle for half a century. This development will help identify these rare donors and help patients in the future.”

Nicole Thornton, Head of IBGRL Red Cell Reference at NHS Blood and Transplant, said: “Resolving the genetic basis for AnWj has been one of our most challenging projects.

“There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world.

“Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms.”

Dr Tim Satchwell, Senior Lecturer at UWE Bristol, who contributed to the study whilst a Research Fellow at the University of Bristol, said: “Mal is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system. Being able to combine our expertise to finally achieve this has brought the whole team a lot of satisfaction".

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Friday, September 20, 2024

Milk research scientist wins global dairy award

A food scientist from the Riddet Institute, Natalie Ahlborn, has wowed judges at an international dairy industry award, placing second in the International Dairy Federation Professor Pavel Jelen Early Career Scientist Prize.

The International Dairy Federation (IDF) is an international authority in the development of science-based standards for the global dairy sector, with the IDF Professor Pavel Jelen Early Career Scientist Prize specifically for scientists who gained their highest degrees three years ago or less.

Ahlborn has been researching processed milk and its effects on digestion and nutrient absorption, as part of the Ministry of Business, Innovation and Employment-funded New Zealand Milk Means More research programme at the Riddet Institute, based at Massey University in Palmerston North.

Pasteurisation, UHT treatment, and homogenisation are commonly used to process milk, and Ahlborn wanted to know what these treatments mean for digestion and nutrient uptake.

She examined milk nutrient digestion and absorption in the gastrointestinal tract, finding that the protein in UHT milk was digested the fastest, followed by the protein in pasteurised homogenised milk, then pasteurised non-homogenised and, finally, raw milk.

Curd formation and stomach emptying of solid matter and lipids were also measured. There were substantial differences in digestion of the fats and solid portions of the milks.

The research has created a fundamental understanding of how processing affects the gastric digestion of milk protein, and how this might contribute to milk’s nutritional outcomes.

Ahlborn said the findings could lead to tailored milk products that deliver superior nutritional value to consumer populations with different nutritional needs, such as those of athletes or the elderly.

“As the global population grows and ages, the need for quality nutrition is paramount, and this research could contribute to meeting this need.”

Ahlborn will receive a printed certificate recognising the achievement and an honorarium of $360. She will attend the IDF World Dairy Summit 2024 to be held in Paris, France, from October 15-18 to collect her award and present her research.

NZ Milk Means More project leader and Ahlborn’s PhD supervisor Professor Warren McNabb said the win is an amazing opportunity for Ahlborn.

“Natalie has done an outstanding job with her research. It’s not every day that a global entity like the IDF takes notice of someone and then pays for them to travel to Paris to receive an award. It’s quite a big deal.”

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Thursday, September 19, 2024

Scientists find new blood group after 50-year mystery

Thousands of lives could be saved around the world after NHS scientists discovered a new blood group system - solving a 50-year-old mystery.

The research team, led by NHS Blood and Transplant (NHSBT) scientists in South Gloucestershire and supported by the University of Bristol, found a blood group called MAL.

They identified the genetic background of the previously known AnWj blood group antigen, which was discovered in 1972 but unknown until now after this world-first test was developed.

Senior research scientist at NHSBT Louise Tilley said the discovery means better care to rare patients can be offered.

Ms Tilley, who has worked on the project for 20 years, told the BBC it is "quite difficult to a put a number" on how many people will benefit from the test. However, the NHSBT is the last resort for about 400 patients across the world each year.

Everyone has proteins outside their red blood cells known as antigens, but a small number might lack them.

Using genetic testing, NHSBT’s International Blood Group Reference Laboratory in Filton have for the first time developed a test that will identify patients missing this antigen.

The test could prove a lifesaver for those who would react against a blood transfusion, and will make it easier to find potential blood developers for this rare blood type.

Philip Brown, who works at the laboratory, was diagnosed with a form of leukaemia about 20 years ago.

He had blood transfusions and a bone marrow transplant - without that, he would have died.

"Anything we can do to make our blood much safer and a better match for patients is a definite step in the right direction," he said.

Head of the laboratory Nicole Thornton said: “Resolving the genetic basis for AnWj has been one of our most challenging projects.

“There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world.

“Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors.

"Such tests can be added to the existing genotyping platforms.”
'World-first test'

Our health reporter Matthew Hill said it was "easy to understate the international significance" of NHSBT in Filton.

"Not only have they developed this world-first test, but also they provide countries across the world with antibodies to allow them to carry out research.

"They are from reference labs in other countries who have already done a lot of work and have got to the point where they have reached their limit of what they can do and then they send their samples to NHSBT," he said.

The head of the lab Nicole Thornton told him: “Often if the labs cannot resolve it we have to do a lot more work to possibly discover a new blood group or a blood group system if its not easily resolvable in our hands.

"And that is where the interesting cases come from. We have some new work in the pipeline at the moment that we think that’s going to lead to some new antigens in current blood systems but also some new blood group systems in addition to the one we have just published."

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Monday, September 16, 2024

When one Chinese national recently petitioned the U.S. Citizenship and Immigration Services to become a permanent resident, he thought his chances were pretty good. As an accomplished biologist, he figured that news articles in top media outlets, including The New York Times, covering his research would demonstrate his "extraordinary ability" in the sciences, as called for by the EB-1A visa.

But when the immigration officers rejected his petition, they noted that his name did not appear anywhere in the news articles. News coverage of a paper he co-authored did not directly demonstrate his major contribution to the work.

As this biologist's close friend, I felt bad for him because I knew how much he had dedicated to the project. He even started the idea as one of his Ph.D. dissertation chapters. But as a scientist who studies topics related to scientific innovation, I understand the immigration officers' perspective: Research is increasingly done through teamwork, so it's hard to know individual contributions if a news article reports only the study findings.

This anecdote made me and my colleagues Misha Teplitskiy and David Jurgens curious about what affects journalists' decisions about which researchers to feature in their news stories.

There's a lot at stake for a scientist whose name is or isn't mentioned in journalistic coverage of their work. News media play a key role in disseminating new scientific findings to the public. The coverage of a particular study brings prestige to its research team and their institutions. The depth and quality of coverage then shapes public perception of who is doing good science. In some cases, as my friend's story suggests, the coverage can affect individual careers.

Do scientists' social identities, such as ethnicity or race, play a role in who gets named?

This question is not straightforward to answer. On the one hand, racial bias may exist, given the profound underrepresentation of minorities in U.S. mainstream media. On the other, science journalism is known for its high standard of objective reporting. We decided to investigate this question in a systematic fashion using large-scale observational data.
The least coverage? Chinese and African names

My colleagues and I analyzed 223,587 news stories from 288 U.S. media outlets, sourced from Altmetric.com, a website that monitors online posts about research papers. The news stories, published from 2011-2019, covered 100,486 scientific papers. For each paper, we focused on authors with the highest chance of being mentioned: the first author, last author and other designated corresponding authors. We calculated how often the authors were mentioned in the news articles reporting their research.

We used an algorithm to infer perceived ethnicity from authors' names. We figured that journalists may rely on such cues in the absence of scientists' self-reported information. We considered authors with Anglo names – like John Brown or Emily Taylor – as the majority group and then compared the average mention rates across nine broad ethnic groups.
Pragmatic factors and language choices

First and foremost, the underrepresentation of scientists with East Asian and African names may be due to pragmatic challenges faced by U.S.-based journalists in interviewing them. Factors like time zone differences for researchers based overseas and actual or perceived English fluency could be at play as a journalist works under deadline to produce the story.

We isolated these factors by focusing on researchers affiliated with American institutions. Among U.S.-based researchers, pragmatic difficulties should be minimized because they're in the same geographic region as the journalists and they're likely to be proficient in English, at least in writing. In addition, these scientists would presumably be equally likely to respond to journalists' interview requests, given that media attention is increasingly valued by U.S. institutions.

This study conceptualizes a quadrant model characterizing four profiles by contrasting university scientists’ multiple goals: research performance and commercialization. Since literature shows that these goals are conflicting but not mutually exclusive, social capital theory is drawn to test the influence of scientists’ bonding, bridging, and linking social capital on their profile affiliation.

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Friday, September 13, 2024

US scientists are leaving academia. That’s bad news for drug companies

New YorkCNN —

Scientists in the United States, especially those in the biomedical fields, are increasingly leaving the world of academia for better-paying industry jobs amid stagnant federal funding and low wages.

It’s a troubling sign for the future of US-based medical research and development at pharmaceutical and biotech companies, which rely on the experimental science housed at universities to develop cutting-edge commercial products.

According to the National Institutes of Health, the number of postdoctoral fellows supported by NIH grants has been steadily falling for more than 20 years, with a significant dip after 2020. The number of postdocs in the biological and biomedical fields has declined 9% between 2018 and 2022, and those in health-related fields have fallen by 8%, according to a survey published on March 20 by the National Science Foundation.

Why are postdoctoral researchers important?

The problem is that postdocs are a critical component of the research and development workforce.

“Science postdocs perform the science,” Donna Ginther, an economist who studies the science labor market at the University of Kansas, told CNN. “They’re actually in the lab doing the work, so they make very important contributions to new scientific discovery.”

Those contributions are part of a long game. Biomedical companies take scientific contributions and, over time, aggregate them into a commercial product. Building on the discovery of mRNA in the 1960’s, the technology behind an mRNA vaccine for humans was in development for decades before the Covid-19 vaccine was first administered in 2020.

“It takes a long time from that first discovery to turn it into a product,” said Ginther.

In 2005, researchers learned that RNA could have immense therapeutic potential, but “found there was no interest” in this discovery, Nobel Prize-winning biochemist Dr. Katalin Kariko told Wired Magazine in 2020.

By using that technology to develop their mRNA vaccines for Covid-19, pharmaceutical companies like Pfizer and Moderna made a windfall in profits. Between 2020 and 2021, Pfizer saw its revenue nearly double. In the same period, Moderna’s total revenue skyrocketed from $803 million to $18.5 billion, astounding growth the company said was “primarily due to commercial sales of (the) COVID-19 vaccine.”

Ginther said most biotech and biomedical companies aren’t concerned with funding basic science like universities.

Why are scientists leaving academic labs?

Interestingly, the number of graduate students — those pursuing master’s degrees and PhDs — in biomedical fields has grown by 22% between 2018 and 2022, according to the NSF survey. And the number of predoctoral students funded by NIH fellowships has increased steadily since 1998.

Experts say these students are increasingly seeking out better paying industry jobs. Unlike academic positions, these roles don’t require postdoctoral research experience.

“There’s no economic benefit (to doing a postdoctoral fellowship),” said Ginther. “If you spend four to six years in a postdoc and then jump into the industry, your starting salary is the same as if we would have just entered into industry automatically.”

The pay gap between academia and industry is also astronomical, which has the added effect of making corporate jobs much more financially attractive to students.

The NIH determines stipend amounts for US citizens in postdoctoral programs. The stipend for a first-year postdoc is roughly $56,000 per year, with marginal yearly wage increases. But in biotech, postdocs and PhD graduates can easily crack six figures.

Ginther served on an advisory committee to the NIH in December, where she and colleagues recommended the NIH increase their stipend amounts by 34% to $70,000 per year.

“The NIH was waiting for its budget and that budget was passed a week ago, so I’m sure they’re having discussions about it right now,” she said. Ginther noted that the federal budget granted to the NIH was flat for fiscal year 2024, which “in a time with rising .

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Thursday, September 12, 2024

A Cure for Multiple Sclerosis? Scientists Say Within Our Lifetime

A generation ago, most people with multiple sclerosis could expect to rely on walkers and wheelchairs or be limited to their bed within 15 years of diagnosis. Today, UC San Francisco’s discoveries are keeping millions with MS healthier for longer – many disability-free. Now, the university is paving the way for an MS cure in our lifetimes.

But the breakthrough almost didn’t happen. “Biologically implausible,” is what the National Institutes of Health’s rejection letter said. It was the late ’90s and UCSF Neurology Professor Stephen Hauser, MD, and team had applied for federal funding for the first clinical trial of the new medicine, rituximab, as a potential MS treatment.

The study wouldn’t just test a new drug, but a revolutionary new theory about MS’ inner workings. So outlandish was the idea that the largest public funder of scientific research said it couldn’t be done.

The rejection “hit like a ton of bricks,” Hauser remembered in his 2023 memoir, The Face Laughs While the Brain Cries. But if Hauser’s team proposed another trial, following conventional wisdom, the institutes assured him there was money.

The message was clear: “Just forget your last 15 years of work, kid, and do what we think.”
‘I decided right there that this would be my life’s work’

Two decades earlier as a young medical resident, Hauser treated 27-year-old Andrea. A recent Harvard Law graduate, Andrea was a rising star in President Jimmy Carter’s administration. Then, as sudden as a lightning strike, her behavior became erratic. By the time Hauser saw her, she was propped up in a hospital bed, the right side of her mouth drooping, saliva pooling at the corner.

MS is a disease of the brain and immune system. Our brains contain a network of billions of neurons, nerve cells that send messages telling our mouth to speak, our legs to move and our lungs to breathe. Each neuron is wrapped in myelin, a protective coating like the plastic sheath around a copper electrical wire. But with MS, our immune system – which normally protects us against germs – mistakes myelin for a foreign invader. This case of mistaken identity prompts an all-out assault. The immune system attacks the myelin, short-circuiting our neurons like frayed power cords.

“Over time, the connections between nerves are lost, nerve cells die. MS robs people of basic functions we take for granted – vision, sensation, motor strength … and sometimes, as with Andrea, even the ability to speak, eat or breathe independently,” Hauser said.

With no effective treatment, there was nothing Hauser could do for Andrea. “I decided right there that this common, crippling disease of young adults would be my life’s work.”

“The federal government has to rely on expert referees to guide funding decisions, and it’s very difficult to turn around entrenched ideas, even if there’s all sorts of wonderful biology behind the new idea,” said Hauser, explaining why he understood the NIH’s initial rejection. “And it’s important that the federal government not spend their resources funding new ideas that most experts feel are unlikely to succeed; this protects us all against the use of public funds to advance crackpot ideas.”

Pharmaceutical company Genentech, co-founded by UCSF professors, agreed to fund what would become a wildly successful trial of the drug as an MS treatment. Rituximab stopped the disease virtually in its tracks, changing the face of MS forever. The breakthrough led to the 2017 development of a second MS medicine, ocrelizumab and then a third, ofatumumab, in 2020, also pioneered by Hauser and his UCSF colleagues working closely with industry partners.

“Beautifully, this is a UCSF story but it also involves great colleagues at other centers across the globe, courageous industry leaders and fantastic philanthropists who believed in high-risk work at a time when traditional funding sources would never be able to support this research,” Hauser said. “And finally, without the thousands of patients who trusted in us and were courageous enough to volunteer for these clinical studies, this progress could never have been made.”

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