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Mixed public opinion on polygenic embryo screening for IVF

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Mixed public opinion on polygenic embryo screening for IVF


Three out of four U.S. adults support the use of emerging technologies that estimate a future child’s likelihood of developing health conditions influenced by multiple genes — such as diabetes, heart disease, and depression — before an embryo is implanted during in vitro fertilization (IVF), according to a new public opinion survey led by researchers at Harvard Medical School.

Results of the survey, to be published May 14 in JAMA Network Open, underscore the need for public education and conversation about the positive and negative implications of these ethically fraught technologies, the researchers said.

Although the approach, known as polygenic embryo screening, is not yet available in most IVF clinics, a few companies have begun offering such estimates — or risk scores — to gauge disease risk, the researchers noted.

“Polygenic embryo screening is largely unregulated in the United States, and without proper context and focused patient education, risk scores can create false expectations,” said first author Rémy Furrer, research fellow in bioethics in the Department of Global Health and Social Medicine in the Blavatnik Institute at HMS.

“This survey rings the alarm that geneticists, behavioral scientists, bioethicists, clinicians, and genetic counselors need to work together to figure out ways to communicate the limitations to people, so they understand what polygenic risk scores do and don’t provide,” he said.

Nearly three-quarters of respondents said they support using such screening to assess the risk of a future child developing a physical or psychiatric condition, such as heart disease, diabetes, or depression — but that number dropped when people were first presented with various concerns for individuals and society.

Far fewer respondents approved the use of the technology to predict traits unrelated to disease, such as intelligence, height, and skin color.

The results suggest that educating people better about the current shortfalls and implications — including regulating the promises that companies can make — will temper optimism and help ensure that as these technologies develop, they will be implemented in scientifically sound, ethical, and equitable ways, the authors said.

How accurate are polygenic risk scores?

Up until now, patients undergoing IVF could choose which embryos to implant based on DNA tests that detect chromosomal abnormalities, such as Down syndrome, and diseases caused by mutations in a single gene, such as cystic fibrosis. Such screening, known as preimplantation genetic testing, is well-established and widely used.

By contrast, polygenic embryo screening estimates probabilities for conditions and traits influenced by many gene variants that each raise or lower risk by a small amount.

Experts disagree on how useful this technology might become in the future, but at present there are clear limitations to accuracy, Furrer said. Polygenic conditions arise from different combinations of genes, environment, and behaviors in ways that aren’t yet fully understood. The American College of Medical Genetics and Genomics has said that polygenic embryo screening is not yet suitable for clinical use.

This gap between the state of the science and the growing availability of such tests compelled Furrer and colleagues to conduct the survey. They hope the results inspire professionals to advocate for more informed dialogue and guidance around these technologies.

“The complexities and limitations of polygenic risk scores are challenging to convey.” Furrer said. “But we need to do so to ensure that people understand the high level of uncertainty that comes with estimating these risks.”

By the numbers

The survey drew from the team’s interviews with IVF patients and reproductive health specialists. Questions included lists of conditions, traits, and potential repercussions that participants were asked to weigh in on. The survey also made clear that polygenic risk scores could be used simply for information, to prepare for a future child, or to select an embryo for implantation.

The first part of the study surveyed more than 1,400 participants representing the wider U.S. population in age, gender, and race/ethnicity. It was conducted between March and July 2023.

Findings showed that:

  • 72 percent of respondents approved of using polygenic embryo screening in general.
  • 17 percent were ambivalent and 11 percent disapproved.
  • 77 percent approved of selecting embryos based on risk of certain physical health conditions.
  • 72 percent approved of selecting embryos based on risk of certain psychiatric health conditions.
  • 36 percent approved of selecting embryos based on likelihood of certain behavioral traits.
  • 30 percent approved of selecting embryos based on likelihood of certain physical traits.
  • 92 percent expressed at least slight concern about polygenic embryo screening leading to false expectations about the future child.
  • About half were “very” or “extremely” concerned about negative outcomes for individuals or society.
  • 82 percent said they would be at least slightly interested in using polygenic embryo screening if they were already undergoing IVF.
  • 30 percent said they would consider undergoing IVF to gain access to polygenic embryo screening.

Approval was higher for using risk scores to prepare for a child than to select an embryo.

Positives and negatives

The second part of the study, conducted from March 2023 to February 2024 with about 200 respondents, placed the list of potential concerns at either the beginning or the end of the survey.

The concerns were:

  • Parents having false expectations about the future child.
  • Promoting eugenic thinking or practices — unethical efforts to select on a wide scale for traits considered desirable.
  • Stigmatizing certain traits and conditions viewed as less desirable.
  • Treating embryos like a product by selecting them based on preferred genetic chances for conditions or traits.
  • Risk scores not being equally relevant for all ethnicities because of the Euro-centric nature of many genetic databases.
  • Unequal access to the technology due to high cost.
  • Low accuracy of genetic estimates for conditions or traits.
  • Reduced diversity of human population.
  • Possibility of nurtured genetics — parents consciously or unconsciously shaping their children’s environments based on the genetic estimates.
  • Confusion over how to interpret and use test results.
  • Guilt over decisions if the child develops a particular condition or trait.
  • Discarding of embryos.
  • Feeling pressured to use the technology.

In the second survey, respondents given the list at the start reported lower overall approval (28 percentage points less) and more uncertainty (24 percentage points higher) about polygenic embryo screening than those who saw the list at the end — a finding that speaks to the importance of education and framing the public conversation.

How to find the right balance

Some of the survey results are nuanced, the authors note, and should not be taken as unqualified public support or rejection of polygenic embryo screening.

“These findings offer an initial glimpse into public opinion, predicated on a limited presentation of the technology,” said Furrer. “Future research must explore how opinions evolve.”

For instance, the team recommends further research into what it means that a majority of respondents approved of polygenic screening for selecting embryos but also expressed strong concerns about sliding into eugenics.

It will also be important to examine the role that personal and group values, such as reproductive freedom and autonomy, play in shaping public attitudes, the authors said.

The authors conclude that the work underscores the need to inform not only the public and IVF patients but also clinicians and genetic counselors, who need to be prepared to answer the rising tide of questions about the potential benefits, present limitations, and concerns surrounding polygenic embryo screening.

Authorship, funding, disclosures

Additional authors are Dorit Barlevy, Stacey Pereira, Shai Carmi, Todd Lencz, and principal investigator Gabriel Lázaro-Muñoz, assistant professor of psychiatry in the Center for Bioethics and Department of Global Health and Social Medicine at HMS.

This work was supported in part by the National Human Genome Research Institute at the National Institutes of Health (grant R01-HG011711). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

All authors reported receiving NIH grants during the conduct of the study. Carmi also reported receiving personal fees from MyHeritage outside the submitted work.



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Early dark energy could resolve cosmology’s two biggest puzzles

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Mixed public opinion on polygenic embryo screening for IVF


A new study by MIT physicists proposes that a mysterious force known as early dark energy could solve two of the biggest puzzles in cosmology and fill in some major gaps in our understanding of how the early universe evolved.

One puzzle in question is the “Hubble tension,” which refers to a mismatch in measurements of how fast the universe is expanding. The other involves observations of numerous early, bright galaxies that existed at a time when the early universe should have been much less populated.

Now, the MIT team has found that both puzzles could be resolved if the early universe had one extra, fleeting ingredient: early dark energy. Dark energy is an unknown form of energy that physicists suspect is driving the expansion of the universe today. Early dark energy is a similar, hypothetical phenomenon that may have made only a brief appearance, influencing the expansion of the universe in its first moments before disappearing entirely.

Some physicists have suspected that early dark energy could be the key to solving the Hubble tension, as the mysterious force could accelerate the early expansion of the universe by an amount that would resolve the measurement mismatch.

The MIT researchers have now found that early dark energy could also explain the baffling number of bright galaxies that astronomers have observed in the early universe. In their new study, reported in the Monthly Notices of the Royal Astronomical Society, the team modeled the formation of galaxies in the universe’s first few hundred million years. When they incorporated a dark energy component only in that earliest sliver of time, they found the number of galaxies that arose from the primordial environment bloomed to fit astronomers’ observations.

You have these two looming open-ended puzzles,” says study co-author Rohan Naidu, a postdoc in MIT’s Kavli Institute for Astrophysics and Space Research. “We find that in fact, early dark energy is a very elegant and sparse solution to two of the most pressing problems in cosmology.”

The study’s co-authors include lead author and Kavli postdoc Xuejian (Jacob) Shen, and MIT professor of physics Mark Vogelsberger, along with Michael Boylan-Kolchin at the University of Texas at Austin, and Sandro Tacchella at the University of Cambridge.

Big city lights

Based on standard cosmological and galaxy formation models, the universe should have taken its time spinning up the first galaxies. It would have taken billions of years for primordial gas to coalesce into galaxies as large and bright as the Milky Way.

But in 2023, NASA’s James Webb Space Telescope (JWST) made a startling observation. With an ability to peer farther back in time than any observatory to date, the telescope uncovered a surprising number of bright galaxies as large as the modern Milky Way within the first 500 million years, when the universe was just 3 percent of its current age.

“The bright galaxies that JWST saw would be like seeing a clustering of lights around big cities, whereas theory predicts something like the light around more rural settings like Yellowstone National Park,” Shen says. “And we don’t expect that clustering of light so early on.”

For physicists, the observations imply that there is either something fundamentally wrong with the physics underlying the models or a missing ingredient in the early universe that scientists have not accounted for. The MIT team explored the possibility of the latter, and whether the missing ingredient might be early dark energy.

Physicists have proposed that early dark energy is a sort of antigravitational force that is turned on only at very early times. This force would counteract gravity’s inward pull and accelerate the early expansion of the universe, in a way that would resolve the mismatch in measurements. Early dark energy, therefore, is considered the most likely solution to the Hubble tension.

Galaxy skeleton

The MIT team explored whether early dark energy could also be the key to explaining the unexpected population of large, bright galaxies detected by JWST. In their new study, the physicists considered how early dark energy might affect the early structure of the universe that gave rise to the first galaxies. They focused on the formation of dark matter halos — regions of space where gravity happens to be stronger, and where matter begins to accumulate.

“We believe that dark matter halos are the invisible skeleton of the universe,” Shen explains. “Dark matter structures form first, and then galaxies form within these structures. So, we expect the number of bright galaxies should be proportional to the number of big dark matter halos.”

The team developed an empirical framework for early galaxy formation, which predicts the number, luminosity, and size of galaxies that should form in the early universe, given some measures of “cosmological parameters.” Cosmological parameters are the basic ingredients, or mathematical terms, that describe the evolution of the universe.

Physicists have determined that there are at least six main cosmological parameters, one of which is the Hubble constant — a term that describes the universe’s rate of expansion. Other parameters describe density fluctuations in the primordial soup, immediately after the Big Bang, from which dark matter halos eventually form.

The MIT team reasoned that if early dark energy affects the universe’s early expansion rate, in a way that resolves the Hubble tension, then it could affect the balance of the other cosmological parameters, in a way that might increase the number of bright galaxies that appear at early times. To test their theory, they incorporated a model of early dark energy (the same one that happens to resolve the Hubble tension) into an empirical galaxy formation framework to see how the earliest dark matter structures evolve and give rise to the first galaxies.

“What we show is, the skeletal structure of the early universe is altered in a subtle way where the amplitude of fluctuations goes up, and you get bigger halos, and brighter galaxies that are in place at earlier times, more so than in our more vanilla models,” Naidu says. “It means things were more abundant, and more clustered in the early universe.”

“A priori, I would not have expected the abundance of JWST’s early bright galaxies to have anything to do with early dark energy, but their observation that EDE pushes cosmological parameters in a direction that boosts the early-galaxy abundance is interesting,” says Marc Kamionkowski, professor of theoretical physics at Johns Hopkins University, who was not involved with the study. “I think more work will need to be done to establish a link between early galaxies and EDE, but regardless of how things turn out, it’s a clever — and hopefully ultimately fruitful — thing to try.”

We demonstrated the potential of early dark energy as a unified solution to the two major issues faced by cosmology. This might be an evidence for its existence if the observational findings of JWST get further consolidated,” Vogelsberger concludes. “In the future, we can incorporate this into large cosmological simulations to see what detailed predictions we get.”

This research was supported, in part, by NASA and the National Science Foundation.



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Plant-derived secondary organic aerosols can act as mediators of plant-plant interactions

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Mixed public opinion on polygenic embryo screening for IVF


A new study published in Science reveals that plant-derived secondary organic aerosols (SOAs) can act as mediators of plant-plant interactions. This research was conducted through the cooperation of chemical ecologists, plant ecophysiologists and atmospheric physicists at the University of Eastern Finland.

It is well known that plants release volatile organic compounds (VOCs) into the atmosphere when damaged by herbivores. These VOCs play a crucial role in plant-plant interactions, whereby undamaged plants may detect warning signals from their damaged neighbours and prepare their defences. “Reactive plant VOCs undergo oxidative chemical reactions, resulting in the formation of secondary organic aerosols (SOAs). We wondered whether the ecological functions mediated by VOCs persist after they are oxidated to form SOAs,” said Dr. Hao Yu, formerly a PhD student at UEF, but now at the University of Bern.

The study showed that Scots pine seedlings, when damaged by large pine weevils, release VOCs that activate defences in nearby plants of the same species. Interestingly, the biological activity persisted after VOCs were oxidized to form SOAs. The results indicated that the elemental composition and quantity of SOAs likely determines their biological functions.

“A key novelty of the study is the finding that plants adopt subtly different defence strategies when receiving signals as VOCs or as SOAs, yet they exhibit similar degrees of resistance to herbivore feeding,” said Professor James Blande, head of the Environmental Ecology Research Group. This observation opens up the possibility that plants have sophisticated sensing systems that enable them to tailor their defences to information derived from different types of chemical cue.

“Considering the formation rate of SOAs from their precursor VOCs, their longer lifetime compared to VOCs, and the atmospheric air mass transport, we expect that the ecologically effective distance for interactions mediated by SOAs is longer than that for plant interactions mediated by VOCs,” said Professor Annele Virtanen, head of the Aerosol Physics Research Group. This could be interpreted as plants being able to detect cues representing close versus distant threats from herbivores.

The study is expected to open up a whole new complex research area to environmental ecologists and their collaborators, which could lead to new insights on the chemical cues structuring interactions between plants.



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Folded or cut, this lithium-sulfur battery keeps going

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Most rechargeable batteries that power portable devices, such as toys, handheld vacuums and e-bikes, use lithium-ion technology. But these batteries can have short lifetimes and may catch fire when damaged. To address stability and safety issues, researchers reporting in ACS Energy Letters have designed a lithium-sulfur (Li-S) battery that features an improved iron sulfide cathode. One prototype remains highly stable over 300 charge-discharge cycles, and another provides power even after being folded or cut.

Sulfur has been suggested as a material for lithium-ion batteries because of its low cost and potential to hold more energy than lithium-metal oxides and other materials used in traditional ion-based versions. To make Li-S batteries stable at high temperatures, researchers have previously proposed using a carbonate-based electrolyte to separate the two electrodes (an iron sulfide cathode and a lithium metal-containing anode). However, as the sulfide in the cathode dissolves into the electrolyte, it forms an impenetrable precipitate, causing the cell to quickly lose capacity. Liping Wang and colleagues wondered if they could add a layer between the cathode and electrolyte to reduce this corrosion without reducing functionality and rechargeability.

The team coated iron sulfide cathodes in different polymers and found in initial electrochemical performance tests that polyacrylic acid (PAA) performed best, retaining the electrode’s discharge capacity after 300 charge-discharge cycles. Next, the researchers incorporated a PAA-coated iron sulfide cathode into a prototype battery design, which also included a carbonate-based electrolyte, a lithium metal foil as an ion source, and a graphite-based anode. They produced and then tested both pouch cell and coin cell battery prototypes.

After more than 100 charge-discharge cycles, Wang and colleagues observed no substantial capacity decay in the pouch cell. Additional experiments showed that the pouch cell still worked after being folded and cut in half. The coin cell retained 72% of its capacity after 300 charge-discharge cycles. They next applied the polymer coating to cathodes made from other metals, creating lithium-molybdenum and lithium-vanadium batteries. These cells also had stable capacity over 300 charge-discharge cycles. Overall, the results indicate that coated cathodes could produce not only safer Li-S batteries with long lifespans, but also efficient batteries with other metal sulfides, according to Wang’s team.

The authors acknowledge funding from the National Natural Science Foundation of China; the Natural Science Foundation of Sichuan, China; and the Beijing National Laboratory for Condensed Matter Physics.



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