Category Archives: Genetic Engineering

The bovine viral diarrhea virus (BVDV) is one of the most dangerous pathogens affecting the health and wellbeing of cattle worldwide, costing the U.S. industry billions of dollars annually. First identified in the 1940s, BVDV can be disastrous to pregnant cows since it can infect developing calves, and often leads to spontaneous abortions and low birth rates.

While some BVDV-infected calves manage to survive, they remain infected for life, and shed massive amounts of virus to other cattle. Moreover, despite the fact that vaccines against the virus have been available for over half a century, they are not always effective in stopping transmission.

Over the past two decades, scientists have managed to identify the main cellular receptor (CD46) and the area where the virus binds to that receptor, causing infection in cattle. Now, a team of researchers led by USDAs Agricultural Research Services (ARS) has used gene-editing technology to slightly alter CD46 so it would not bind the virus, yet retain all its normal functions in bovines.

After successfully testing this idea in laboratory cell cultures, the scientists collaborated with Acceligen a company specializing in precision breeding technology aiming to improve animal welfare and resistance to disease to genetically edit cattle skin cells in order to develop embryos carrying the altered gene. The team then transplanted the embryos into surrogate cows to assess whether this approach could reduce viral infection in live animals.

The technique proved to be highly successful and the first CD46 gene-edited calf, named Ginger, was born healthy on July 19, 2021. After keeping the calf under observation for a few months, the experts housed it for a week with a BVDV-infected dairy calf which was born shedding the virus.

Gingers cells displayed significantly reduced susceptibility to the virus, resulting in no observable adverse health effects. Although these results are highly promising, the scientists will continue to closely monitor Gingers health and ability to produce and raise her own calves.

This proof-of-concept study demonstrates the revolutionary possibilities of gene-editing technology in reducing the burden of BVDV in cattle.

At the same time, since BVDV infection puts calves at risk for secondary bacterial infections, using gene-editing technology to breed cattle resistant to this virus may also diminish the need for antibiotics in agriculture.

The research is published in the journal PNAS Nexus.

Gene editing is a group of technologies that gives scientists the ability to change an organisms DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed.

One of the most well-known is CRISPR-Cas9, which stands for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays.

The CRISPR arrays allow the bacteria to remember the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.

In the lab, scientists create a small piece of RNA with a short guide sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location.

Although Cas9 is the enzyme that is used most often, other enzymes (like Cpf1) can also be used. Once the DNA is cut, researchers use the cells own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

Gene editing is considered a type of genetic engineering. Other methods for genetic modification include gene targeting, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs).

Applications of gene editing technologies are vast and include correcting genetic defects, treating and preventing the spread of diseases, and improving crops. However, it also raises ethical questions, particularly when it comes to editing the human genome. For example, there are concerns about its potential use in creating so-called designer babies with specified traits, such as intelligence or athletic ability.

There are also potential risks, such as off-target effects (unintended changes to DNA), and the long-term effects of gene editing are still largely unknown. Its a rapidly evolving field with enormous potential, but it also requires careful regulation and oversight.

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By Andrei Ionescu, Earth.com Staff Writer

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

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Gene editing technology used to produce disease-resistant calf - Earth.com

Neanderthals were equipped with tall noses that could warm and moisten the cold and dry air around them in chilly climates an adaptation that may be the result of natural selection.

These sizable schnozzes were likely helpful to Neanderthals; once anatomically modern humans (Homo sapiens) left Africa and joined Neanderthals up north in Eurasia, the two mated, with Neanderthals gifting Homo sapiens their bigger-nose genes, a new study finds.

Scientists made the discovery after analyzing DNA taken from more than 6,000 volunteers recruited from Brazil, Colombia, Chile, Mexico and Peru who had Latin American, mixed European, Native American or African heritage, and compared their genetic information to photographs of their faces, according to a study published May 8 in the journal Communications Biology (opens in new tab).

After measuring the distances between different points on each face, such as the height of a person's nose, the researchers compared those data to see if those characteristics were associated with certain genetic markers, according to a statement (opens in new tab).

The researchers successfully identified 33 new genome regions that corresponded with facial features. One in particular, ATF3, not only had Neanderthal origins but also defined nose height. They found that study participants with Native American ancestry "had genetic material in this gene that was inherited from the Neanderthals, contributing to increased nasal height," according to the statement.

Related: Human and Neanderthal brains have a surprising 'youthful' quality in common, new research finds

"It has long been speculated that the shape of our noses is determined by natural selection; as our noses can help us to regulate the temperature and humidity of the air we breathe in, different shaped noses may be better suited to different climates that our ancestors lived in," lead author Qing Li (opens in new tab), a faculty member in the Department of Environmental Science and Engineering at Fudan University in Shanghai, said in the statement. "The gene we have identified here may have been inherited from Neanderthals to help humans adapt to colder climates as our ancestors moved out of Africa."

In 2021, the same team of researchers conducted a related study (opens in new tab) that identified a gene that influenced lip shape. That gene, called TBX15, was inherited from the Denisovans, modern-human relatives who lived in Asia and went extinct approximately 30,000 years ago. The Denisovans interbred with Homo sapiens, passing along this genetic attribute. By examining data from this previous study, the researchers discovered that, like Native Americans, East Asians were also more likely to have the ATF3 nose gene.

So what was the benefit of having a taller nose thousands of years ago?

"When you live in colder climates, your nose gets narrower so that it can warm cold air before it reaches the lungs," study co-author Kaustubh Adhikari (opens in new tab), a statistical geneticist at University College London, told Live Science. "We think that when [Homo sapiens] came into colder regions where Neanderthals were already living, they bred with them and they passed along these [genetic] benefits to their children, which helped give them a leg up with adaptation."

Read more:
Neanderthals passed down their tall noses to modern humans ... - Livescience.com

Underneath the rubbery skin of a squid, youll find a community of cells and muscles that work together to create the color and texture changes these animals are known for. This buzzing cellular network is difficult to study, however, and marine biologists and other researchers failed to cultivate a squids skin cells in a laboratory setting for decades.

Now, thanks to recent work done at the University of California, Irvine, a workaround for culturing similar skin cells has been achieved.

The researchers used genetic engineering, advanced 3D microscopy and computational modeling to generate and study human cell cultures with tunable transparency. They believe their engineered cells will shed light on how wild squids turn transparent and potentially also offer new medical imaging methods.

Squids and octopuses rely on three different cell types within their skin to change color. There are cells that reflect light with narrowband reflection called iridophores, begins lead researcher and UC Irvine professor Alon Gorodetsky.

Iridophores reflect light at different wavelengths, and can change color depending on the angle of light. Previous research has found that when looked at from above, for example, an iridophore may appear blue but from the side, it looks red.

Cephalopods also rely on tiny sacs of pigmented cells called chromatophores. The colors are precisely layered, with yellow over red over brown, says Leila Deravi, a professor at Northeastern University who was not involved in the study.

When a cephalopod decides to change color, it contracts or expands adjoining muscle cells to compress or open the chromatophore changing its shape and how it reflects light.

But Gorodetsky and his team focused explicitly on the third type of cell, called leucophores, which scatter light. They have broadband scattering across the visible spectrum, he says.

When the cells reflect light, leucophores appear white. According to Shu Yang, a professor at the University of Pennsylvania, these types of cells are essential because they provide white contrast for the highly pigmented iridophores and chromatophores.

As a result, leucophores ensure a better color match to the environment, which is necessary for creating successful camouflage.

Read More: 4 Hidden Ways Animals Camouflage Themselves

To create this white color, leucophores rely on particles from a specific protein called reflectin. Their assembly state whether clustered or more separated can cause cells to become more opaque or transparent, depending on the immediate surroundings.

To Gorodetsky and his team, the reflectin proteins seemed the perfect biomolecule for forming similar particles in mammalian (human) cells. Unfortunately, the COVID-19 pandemic broke just as the UC Irvine researchers were working on expressing these reflectin proteins.

Forced to work remotely, the scientists used various types of computational modeling and an advanced microscopy technique called holotomography to study the effects of reflectins in mammalian cells.

We have gained a detailed understanding of the self-assembly of these nanoparticles inside cells using holotomography, which is a technique that allows you to visualize the cell in three dimensions, Gorodetsky says. And that gave us insight into the assembly state of these light-reflecting particles inside the cell and how that state can change.

Once pandemic regulations eased off enough to return to the laboratory, the researchers used various other methods to confirm and reinforce their experiments.

Read More: Some Aquatic Species Evolved See-Through Bodies for Camouflage

Gorodetsky and his team genetically engineered the self-assembling reflectin proteins in stable mammalian cells. They then tested the response of the nanostructures to changes in salt concentration in the surrounding environment, to mimic the habitat of cephalopods.

During these tests, the researchers found their cell cultures maintained high viability even when expressing large amounts of the reflectin proteins. In a saltier solution, as the reflectin proteins clumped together, the cells scattered more light and became more opaque.

This is an incredible engineering advancement, Deravi says, being able to genetically engineer cephalopod-specific proteins and protein geometries in composition to mammalian cells. That means you can think about making designer cells with functions they werent originally evolved to do.

In a recent press release, Gorodetsky explained that these developments could offer a way to study cells in real time without bleaching or hurting the sample. Additionally, in a media briefing held by the American Chemical Society, he mentioned potential advancements to medical imaging.

This can be great for imaging live mammalian cells to see how theyre surviving, Deravi says.

Squid camouflage continues to inspire both research and science fiction in tandem.

H.G. Wells proposed that you could make The Invisible Man by matching the refractive index to the surroundings and eliminating all the pigments that give color, Gorodetsky says.

Some science fiction characters even seem to mimic these mammalian cells expressing reflectin.

There was an awesome scene in X-Men: Days of Future Past where they showed how Mystiques skin cells would work, Gorodetsky continues. And it showed that they were filled with these little nanoparticles, which would change their assembly state or change the color.

While Gorodetsky and his team did use human cells to culture the reflectin proteins, he emphasizes that the reflectin proteins are not yet ready for human subjects. In other words, we cant create invisible men or Mystiques using this technology yet.

Read More: Sneaky Deep-Sea Camera Captures Footage of Elusive Giant Squid

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Squid Camouflage Inspires Human Invisibility: Is it Possible? - DISCOVER Magazine

Transparency Market Research

North America to provide significant mice model technologies market opportunities to regional and global manufacturers. High incidence of genetic disorders worldwide has led the significant Research and Development investment in genetic testing and a rise in the adoption of CRISPR technology in the healthcare industry.

Wilmington, Delaware, United States, May 16, 2023 (GLOBE NEWSWIRE) -- The global mice model technologies market stood at US$ 1.6 billion in 2022, and is projected to reach US$ 3.2 billion in 2031. The industry is anticipated to expand at a CAGR of 7.4% between 2023 and 2031.

Personalized medicines are highly preferred for treating many genetic diseases. Mice models help facilitate the development of personalized medicines. Humanized mice models are also gaining popularity in the study of personalized medicines. Especially in cancer research, personalized mice models can be created by implanting a piece of the patients tumor in the immune-compromised mice. Mice can then be tested for response to various personalized cancer drugs. Studies yield promising personalized drug therapies for cancer.

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Pharmaceutical companies have also been reported to use mouse models derived from cancer cell lines to test and improve the effectiveness of new anticancer drugs. Rising demand for personalized medicines would thus drive the demand for mice models in research studies.

Recent mice model technologies market size trends indicate that with the introduction of emerging gene editing techniques particularly CRISPR/Cas9, companies have witnessed tremendous opportunities. Unmet need for efficacious therapeutics for infectious disease, diabetes, and oncology has spurred the commercialization of NOD SCID gamma mouse, found the TMR analysts. Emergence of mouse xenograft models for use in human cancer therapeutics research is a notable case in point, which will boost the future market outlook for mice model technologies.

Story continues

Significant decline in the application of the mice model in drug development apart from COVID-19 because many countries had been in lockdown and have suspended trade with other countries, implemented travel restrictions, etc., leading to declining in market capitalizations of major companies across the world, along with a decline in industrial production and pre-clinical trial which will negatively impact market growth.

Global Mice Model Technologies Market: Growth Drivers

Prevalence of chronic diseases is steering the need for advancing biomedical research strategies. Growing use of mice models in modeling human diseases is propelling strides in the mice model technologies market.

Advent of CRISPR-based techniques and a host of advanced molecular genome-altering technologies has created enormous opportunities. Techniques and technologies are successfully used for creating genetically engineered mouse models.

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Key Takeaways of Market Report

Global mice model technologies market to generate absolute dollar opportunity worth US$ 3.2 billion until 2031.

Global mice model technologies market from 2022 to 2031 is 7.4%

Global mice model technologies market is currently valued at US$ 1.69 billion in 2022.

Global mice model technologies market stood at US$ 1.6 billion in 2021.

Market value of the global mice model technologies market from 2018 to 2022 is 6.89%

North America is said to have a 6.2% market CAGR with the United States being subject to the adoption of mice model technologies at a higher rate.

The Asia-Pacific is expected to grow at a rapid rate of CAGR with 5.4% in the mice model technologies market going forward with China leading from the front.

North America is said to have a 40% market share being subject to the adoption of mice model technologies at a higher rate.

Global Mice Model Technologies Market: Regional Landscape

North America held a key share of the global mice model technologies market in 2021. Enormous research in gene editing technologies over the years and the adoption of new genetic engineering techniques notably CRISPR generated substantial revenue streams in the regional market.

Asia Pacific is estimate to be a lucrative market. Growth is fuelled by investments in biomedical research and drug discovery projects. Cutting-edge research in COVID-19 for the development of effective and safe vaccines and treatments opened up unprecedented opportunities for players in the Asia Pacific mice model technologies market.

Global Mice Model Technologies Market: Key Players

StrategiesGemPharmatech announced that it had entered into a strategic license agreement with Charles River Laboratories, Inc. for exclusive distribution of its next generation NOD CRISPR prkdc IL2r gamma (NCG) mouse lines in North America

AcquistionsCharles River Laboratories signed an agreement to breed, distribute, market, and sell Hera BioLabs SRG rat to the global preclinical research community. Unlike other immunodeficient model created through knockout mutations in the Rag2 and IL2R gamma genes that results in mature B, T, and NK, cell efficiencies.DevelopmentsCharles River Laboratories inked a licensing deal with Crown Bioscience, a drug discovery and development services provider, for expanded access to the Zucker Diabetic Sprague- Dawley (ZDSD) rat model

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Global Mice Model Technologies Market: Segmentation

Technology

CRISPR Knockout

CRISPR Knockin

Random Insertions

Large, Targeted Insertions

ES Cell Modification (Homologous Recombination)

Others

End-user

Pharmaceutical Companies

Biotechnology Companies

Academic and Research Facilities

Contract Research and Manufacturing Organizations

Regions

North America

Latin America

Europe

Asia Pacific

Middle East and Africa

About Transparency Market Research

Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. The firm scrutinizes factors shaping the dynamics of demand in various markets. The insights and perspectives on the markets evaluate opportunities in various segments. The opportunities in the segments based on source, application, demographics, sales channel, and end-use are analysed, which will determine growth in the markets over the next decade.

Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision-makers, made possible by experienced teams of Analysts, Researchers, and Consultants. The proprietary data sources and various tools & techniques we use always reflect the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in all of its business reports.

Contact:Nikhil SawlaniTransparency Market Research Inc.CORPORATE HEADQUARTER DOWNTOWN,1000 N. West Street,Suite 1200, Wilmington, Delaware 19801 USATel: +1-518-618-1030USA Canada Toll Free: 866-552-3453Website:https://www.transparencymarketresearch.com Blog:https://tmrblog.com Email:sales@transparencymarketresearch.com

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Mice Model Technologies Market Poised for 7.4% CAGR Growth, Reaching USD 3.2 Bn by 2031 | Transparency Market Research - Yahoo Finance

A person walks next to the Google Cloud logo at the Mobile World Congress (MWC) in Barcelona, Spain February 27, 2023.

Nacho Doce | Reuters

Google Cloud on Tuesday launched two new AI-powered tools that aim to help biotech and pharmaceutical companies accelerate drug discovery and advance precision medicine.

One tool, called the Target and Lead Identification Suite, is designed to help companies predict and understand the structure of proteins, a fundamental part of drug development. Another, the Multiomics Suite, will help researchers ingest, store, analyze and share mass amounts of genomic data.

The new developments mark Googles latest advancement in the red-hot AI arms race, where tech companies are competing to dominate a market that analysts believe could someday be worth trillions. The company has faced pressure to showcase its generative artificial intelligence technology since the public release of OpenAIs ChatGPT late last year.

Google announced its generative chatbot Bard in February. Shares of its parent company Alphabet rose 4.3% last week after Google unveiled several AI advancements at its annual developer conference.

The two new Google Cloud suites help address a long-standing issue in the biopharma industry: the lengthy and costly process of bringing a new medicine to the U.S. market.

Drug companies can invest anywhere from a few hundred million dollars to more than $2 billion to launch a single drug, according to a recent Deloitte report. Their efforts arent always successful. Medicines that reach clinical trials have a 16% chance of being approved in the U.S., another Deloitte report says.

That hefty cost and bleak success rate is accompanied by an extensive and tedious research process that typically lasts about 10 to 15 years.

The new suites will save companies a statistically significant amount of time and money throughout the drug development process, said Shweta Maniar, Google Clouds global director of life sciences strategy and solutions. Google did not provide CNBC with specific figures.

We're helping organizations get medicines to the right people faster, Maniar told CNBC in an interview. I am personally very excited, this is something that myself and the team have been working on for a few years now.

Both suites are widely available to customers starting Tuesday. Google said the cost will vary depending on the company. Several businesses, including Big Pharma's Pfizer and the biotech companies Cerevel Therapeutics and Colossal Biosciences, have already been using the products.

The Target and Lead Identification Suite aims to streamline the first key step of drug development, which is identifying a biological target that researchers can focus on and design a treatment around, according to Maniar.

A biological target is most commonly a protein, an essential building block of diseases and all other parts of life. Finding that target involves identifying the structure of a protein, which determines its function, or the role it plays in a disease.

If you can understand the role, the protein structure and role, now you can start developing drugs around that, Maniar said.

But that process is time-consuming and often unsuccessful.

Scientists can take around 12 months just to identify a biological target, according to a widely followed guidance manual for drugmakers posted in a database run by the federal National Library of Medicine.The two techniques researchers traditionally use to determine protein structures also have a high rate of failure, according to Maniar.

She also said its difficult for traditional technologies to increase or decrease the amount of work they do based on demand.

Google Clouds suite has a three-pronged approach for making that process more efficient.

The suite allows scientists to ingest, share and manage molecular data on a protein using Google Clouds Analytics Hub, a platform that lets users securely exchange data across organizations.

Researchers can then use that data to predict the structure of a protein with AlphaFold2, a machine learning model developed by a subsidiary of Google.

AlphaFold2 runs on Googles Vertex AI pipeline, a platform that allows researchers to build and deploy machine learning models faster.

In minutes, AlphaFold2 can predict the 3D structure of a protein with more accuracy than traditional technologies and at the scale researchers need. Predicting that structure is critical because it can help researchers understand a proteins function in a disease.

The final component of Google Clouds suite helps researchers identify how the proteins structure interacts with different molecules. A molecule can become the basis for a new drug if it changes that proteins function and ultimately demonstrates the ability to treat the disease.

Researchers can use Google Cloud's high-performance computing resources to find the most promising molecules that could lead to the development of a new drug, according to a press release on the new tools. Those services provide the infrastructure companies need to accelerate, automate and scale up their work.

Cerevel, which focuses on developing treatments for neuroscience diseases, typically has to screen a large library of 3 million different molecules to find one that will produce a positive effect against a disease, according to Chief Scientific Officer John Renger. He called that process "complicated and involved and expensive."

But Renger said the company will be able to weed out molecules faster using Google Cloud's suite. Computers will take care of screening molecules and help Cerevel "get to an answer really quickly," he said.

Renger estimates Cerevel will save at least three years on average by using the suite to discover a new drug. He said it's difficult to estimate how much money the company will save, but emphasized that the suite cuts down on the resources and manual labor typically required to screen molecules.

"What it means is we can get there faster, get there cheaper and we can get to drugs to patients much more quickly without as many failures," he told CNBC.

Cerevel has been working with Google for more than a month to further understand the suite and determine how the company will use it. But Renger hopes Cerevel will "be at a place where we get some results" in the next month.

Google Clouds second solution, the Multiomics Suite, aims to help researchers tackle another daunting challenge: genomic data analysis.

Colossal Biosciences, a biotechnology company that aims to use DNA and genetic engineering to reverse extinction, has been using the Multiomics Suite in its research.

As a startup, Colossal did not have the internal infrastructure necessary to organize or decipher massive quantities of genomic data. One human genome sequence alone requires more than 200 gigabytes of storage, and researchers believe that they will need 40 exabytes to store the worlds genomic data by 2025, according to the National Human Genome Research Institute.

The institute estimates that five exabytes could store every word ever spoken by humans, so building the technology to support genomic data analysis is not a small task.

As such, the Multiomics Suite aims to provide companies like Colossal with the infrastructure they need to make sense of large amounts of data so they can spend more time focusing on new scientific discoveries.

If we had to do everything from scratch, I mean, that's the power of Google Cloud, right? Colossals vice president of strategy and computational sciences, Alexander Titus, told CNBC in an interview. We dont have to build that from scratch, so that definitely saves us time and money.

Researchers ability to sequence DNA has historically outpaced their ability to decipher and analyze it. But as technology has improved in recent years, genomic data has unlocked new insights into areas like the genetic variations associated with disease.

Google Clouds Maniar said it could ultimately aid in the development of more personalized drugs and treatments. In 2021 alone, two-thirds of drugs approved by the Food and Drug Administration were supported by human genetics research, according to a paper published in the journal Nature.

Maniar believes the Multiomics Suite will help encourage further innovation.

Ben Lamm, CEO of Colossal, said the Multiomics Suite is the reason the company has been able to carry out research on any reasonable timeline. Colossal started piloting Google's technology late last year, and as a result, Lamm said the company is on target to produce a woolly mammoth by 2028.

Without the Multiomics Suite, Lamm said he thinks the company would have been set back by over a decade.

We would not be anywhere near where we are today, he said.

Prior to using Google Clouds suite, much of Colossals data management was done manually using spreadsheets, Lamm said.

He said it would have been a massive burden on the company to try to build the more complex tools it needed for research.

We're no longer in small data when it comes to biology, said Colossals Titus. We're thinking on the scale of how do we get insights into 10,000, 20,000, 10 million years of evolutionary history? And those questions just aren't answered without scalable computing infrastructure and tools like cloud computing and Multiomics.

Correction: Scientists can take around 12 months just to identify a biological target, according to a widely followed guidance manual for drugmakers posted in a database run by the federal National Library of Medicine. An earlier version misstated the attribution.

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Google Cloud launches A.I.-powered tools to accelerate drug discovery, precision medicine - CNBC

Emails offer a glimpse into the outsized influence of a small group of scientists. (Photo credit: Unsplash)

Scientists with connections to the Wuhan Institute of Virology including Anthony Fauci steered the U.S. national security state away from hypotheses about the origins of COVID-19 that could implicate their research, emails obtained through the Freedom of Information Act show.

Their sphere of influence spanned the intelligence community and the White House.

On February 3, 2020, scientists tied to high risk coronavirus research in Wuhan joined a call with national security officials about how to uncover how an exceptionally infectious virus had emerged from that city.

The call included officials with the Federal Bureau of Investigation, the Office of the Director of National Intelligence and the White Houses Office of Science and Technology Policy, an email obtained by U.S. Right to Know shows.

The intelligence communitys premature assessment that COVID-19 was a natural virus has in turn been wielded by Fauci and by other virologists to minimize the lab leak theory.

The call shows the apparent power of a small clique of scientists to cloud the publics understanding of the pandemic.

The Wuhan Institute of Virologys two closest collaborators, EcoHealth Alliance President Peter Daszak and University of North Carolina virologist Ralph Baric, were on the call.

Daszak runs the intermediary organization that shepherded funds from the National Institutes of Health to the Wuhan lab complex.

Baric is a coronavirologist who innovated engineering techniques and applied them to viruses prospected in the wild by the Wuhan lab. Baric despite developing undetectable genetic engineering methods nicknamed no see um after the barely perceptible flies found in the Southeast apparently helped persuade the intelligence community that the novel virus betrayed no signs of engineering.

Facilitated by the National Academies of Sciences, Engineering, and Medicine, the purpose of the Feb. 3 call was to respond to misinformation.

Thank you for participating in todays meeting of experts to discuss and identify what data, information and samples are needed to understand the evolutionary origins of 2019-nCoV and more effectively respond to the outbreak and resulting misinformation, wrote Andrew Pope, director of the board on health sciences policy for the National Academies.

Fauci briefed the group on NIAIDs perspective, the agenda shows. Faucis National Institute of Allergy and Infectious Diseases, or NIAID, had underwritten Daszak and Barics work.

The agenda shows that the Feb. 3 call was prompted in part by a flawed and ultimately withdrawn preprint alleging similarities between the genome of SARS-CoV-2 and HIV, which had set off alarm bells in the infectious diseases community.

Its also clear that rumors about the Wuhan Institute of Virology had already begun swirling on Chinese social media.

The discussion was co-led by Fauci, director of the White Houses Office of Science and Technology Policy Kelvin Droegemeier, and Chris Hassell, who in addition to serving as senior science advisor to the Department of Health and Human Services also serves as the chair of the secret committee that oversees gain-of-function research with pandemic potential.

Contemporaneous emails show that Fauci was discussing the apparent connections between NIAID and gain-of-function research in Wuhan with his boss, NIH Director Francis Collins. Fauci was routinely meeting with top national security officials at that time, including in the White House Situation Room, his schedule shows.

Two days prior, Fauci and Collins had discussed the matter with a small group of virologists in a confidential call. Those virologists went on to write a highly influential letter which prompted news organizations around the world to prematurely dismiss the lab leak hypothesis as a conspiracy theory.

One of those virologists, Kristian Andersen with Scripps Research Institute, also participated in the Feb. 3 call.

Emails previously reported by U.S. Right to Know show that Andersen dismissed the idea of an engineered virus to the National Academies group as crackpot. Yet days later he insisted in a separate email that the scientific evidence was not conclusive enough to have high confidence in either the natural or lab hypotheses.

Congress is investigating the matter.

Despite the complexity of the question at hand, the National Academies group had wrapped up its work within a few days.

The letter that resulted from the Feb. 3 call from the National Academies to the White Houses Office of Science and Technology Policy assumed a natural origin.

The possibility of the virus emanating from research which scientific organizations and U.S. intelligence elements now believe to be possible was subsequently dismissed, according to Daszak.

Daszak seemed to think that this National Academies letter together with the letter coauthored by Andersen were enough to dissuade the White House from exploring a possible lab origin.

I dont think this [National Academies] committee will be getting into the lab release or bioengineering hypothesis again any time soon White House seems to be satisfied with the earlier meeting, paper in Nature and general comments within [the] scientific community, Daszak told Baric.

State Department intelligence unit

A few weeks later, Baric may have briefed the State Departments analysts, another email shows.

Barics gain-of-function research was at the center of speculation about a possible lab origin.

Barics research had privately alarmed Fauci and Andersen. Fauci met with Baric nine days after the Feb. 3 call, Faucis schedule shows. They discussed chimeras, or engineered viruses, according to virologists close to Baric.

Yet emails obtained from the State Department appear to show that Baric was asked to brief the State Departments Bureau of Intelligence and Research about the pandemics possible origins.

The briefing coincided with the premature letter debunking the idea that SARS-CoV-2 was engineered coauthored by Andersen, which published on March 17.

Baric apparently received several emails inviting him to participate in an analytic exchange between March 23 and March 25.

The Bureau of Intelligence and Research briefing occurred on March 26.

U.S. scientists say available genomic evidence shows that the SARS-CoV-2 virus probably emerged naturally in an animal before crossing to humans and was not engineered in a lab, the write-up of the briefing read.

Barics apparent inclusion on the call is remarkable because he innovated viral engineering techniques that do not reveal any scars or signs of engineering.

David Feith, former U.S. Deputy Assistant Secretary of State for East Asian and Pacific Affairs, said in sworn testimony to Congress last month that concerns about conflicts of interest skewing the briefing were valid, but that he was precluded from naming which virologists participated.

Feith said that the experts on the call stressed the good quality and robust biosafety and biosecurity programs of Chinas virology labs.

Baric would later express concerns about coronavirus gain-of-function research occurring in BSL-2 conditions at the Wuhan Institute of Virology, lower than the BSL-4 conditions required for the most dangerous pathogens.

Feith described the State Department call as diversionary in his Congressional testimony.

Officials and experts who could have helped equip their colleagues (and the public) with the appropriate background to understand a novel and grave situation and weigh probabilities accordingly instead overwhelmingly deflected and denied, Feith said.

Red Dawn

Baric prematurely assured leading infectious diseases experts that COVID could not have been engineered through more informal channels as well.

The Red Dawn email chain in early 2020 consisted of speculation about the unfolding pandemic and included active and former officials from across several departments and agencies, including HHS, CDC, the Department of Homeland Security, the Veterans Affairs Department and the Pentagon.

Someone on the email chain asked whether restriction sites along the viral genome suggested the pathogen was artificial.

There is absolutely no evidence that this virus is bioengineered, Baric responded.

IC assessment

In late April 2020, the Office of the Director of National Intelligence released an unusual statement that the intelligence community concurred with the wide scientific consensus that the virus was not engineered, a statement that appeared to echo the conclusions of the Feb. 3 and March 26 briefings.

A majority of the views now is that it was natural, it was organic, said Defense Secretary Mark Esper.

In fact, a scientific consensus on this matter did not exist then and does not exist now.

Even so, the idea that SARS-CoV-2 could not be engineered also found its way into the 90-day review that the intelligence community concluded in August 2021.

Most agencies also assess with low confidence that SARS-CoV-2 probably was not genetically engineered; however, two agencies believe there was not sufficient evidence to make an assessment either way, the declassified assessment reads.

U.S. Right to Know obtained documents reported in this article through Freedom of Information Act requests to the Department of Health and Human Services and the State Department. All of the documents obtained in the course of our investigation into the origins of Covid-19 can be reviewed here.

With reporting by Hana Mensendiek

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Rice cereal is a staple in many American babies diets, and is often the first solid food an infant eats. In recent years, however, it has also become one of many baby foods that has been raising alarm among lawmakers and parents.

Most cultivated rice grows submerged in paddy fields, primarily in South and Southeast Asia, although it is also grown in the United States and many other countries. These flooded fields provide a cool, fertile environment for a healthy crop, but that same environment also allows contamination from toxic heavy metals, including arsenic, cadmium, lead, and mercury.

At least some heavy metals appear to harm brain development and cognition; and have also been linked to ailments including lung disease, kidney disease, skin lesions, and cancer. Heavy metal exposure is especially dangerous for infants because, compared to adults, they eat more food relative to their body weight and their diet is less varied. Babies are also particularly sensitive to the toxic effects of heavy metals because their bodies are still developing.

In February 2021, the U.S. House Oversight and Reform Subcommittee on Economic and Consumer Policy released a report on heavy metals in baby food produced by several of the countrys largest manufacturers. The 59-page document ended with a call for immediate action from the Food and Drug Administration. Two months later, the FDA announced the Closer to Zero initiative, which uses an iterative approach to reduce heavy metal exposure among babies and children. The FDA issued draft guidance on lead in fruit and vegetable juice in April 2022 and in baby food more broadly in January 2023. Action plans for arsenic, cadmium, and mercury arent scheduled to be completed until 2024 at the earliest.

In the meantime, botanists, soil chemists, and plant geneticists who have long worked to reduce heavy metals in the food supply continue to look for potential solutions, from new land management practices to nano-sized fertilizers to genetic engineering. Not all of these technologies are available yet; however, even when they are, eliminating heavy metals entirely wont be easy.

Still, some experts are optimistic about the possibilities. While there is no single magic bullet that can address this problem, said Om Parkash Dhankher, a professor of crop biotechnology at the University of Massachusetts Amherst, there are lots of technologies and practices that farmers can use.

HHeavy metals are naturally present in the Earths crust and make their way into aquifers and rivers when water travels through underground rock formations and dissolves the toxic elements. Arsenic, for example, exists in high levels in the groundwater of the U.S., China, and India. Agricultural practices have also contributed to heavy metal contamination. The U.S. has led the world in the use of arsenic for agriculture and industry, and while insecticides with lead and arsenic were banned in the 1980s, soil, paddy water, and rice grains still have detectable levels of the toxins.

These contaminants get sucked up by the roots of a rice plant, which absorb nutrients through proteins in their cell walls. According to Parkash, arsenic essentially hijacks these pathways. As the plant grows, arsenic travels from the roots into the leaves and grains.

Scientists including Parkash are looking for ways to stop arsenic from hijacking the plants to begin with. One approach is to apply more sulfur to paddy soils, which can bind to toxic metals and make them more difficult to absorb.

Heavy metal exposure is especially dangerous for infants because, compared to adults, they eat more food relative to their body weight and their diet is less varied.

In recent years, Parkash and Jason White, who directs the Connecticut Agricultural Experiment Station, have been researching this process at a very small scale. Given how sulfur binds to toxic metals, Parkash and White have looked into ways that nanotechnology which involves manipulating materials at the scale of billionths of a meter could be used for soil remediation. In a recent paper, they found that rice plants treated with both inorganic arsenic, the elements more toxic form, and nanosulfur accumulated nearly a third less of the toxin in root tissue than plants exposed to inorganic arsenic alone.

Other alterations to a field can help, too. Wild plants like water spinach and water celery also slurp up nutrients and toxins, and scientists have studied intercropping rice paddies to help remove contaminants. When these aquatic vegetables are grown alongside rice, overall concentrations of arsenic in the soil decrease and the wild plants absorb the arsenic. Certain species of bacteria can tolerate high levels of arsenic, lead, mercury, and cadmium, and some bacteria have been found to mitigate the toxic effects these heavy metals have on plants. Other microorganisms can reduce arsenic concentrations in crops. Scientists have also genetically engineered bacteria to produce a specific protein that boosts their ability to break down arsenic.

Some of these approaches have yet to be applied in large-scale interventions beyond the lab. Scientists dont even think about extension, said Ganga Hettiarachchi, a soil and environmental chemistry scientist at Kansas State University, referring to a century-old partnership with the U.S. Department of Agriculture and land-grant universities to translate science for practical application in farms and food production. When it comes to the newest research on soil and land management, Hettiarachchi worries that farmers might not be aware of how to apply the latest research. But she is optimistic: I do see that its changing.

Some research on heavy metals in rice cant yet be applied in the field though. Genetic engineering of rice itself, to help the plant block heavy metals, has proven difficult, Shannon Pinson, a plant geneticist at the USDAs Agricultural Research Service, told Undark. There is no genetically modified rice in commercial production in the U.S., although Pinson said that the technology has been a useful research tool for understanding how plants take up heavy metals. For example, her research suggests arsenic accumulation is not controlled by a single gene, but rather many genes with individually small effects.

Not all rice varieties are the same, though, and some take up more arsenic and heavy metals than others. In a 2015 article, Pinsons team examined 1,763 rice cultivars from around the world and compared concentrations of both organic and inorganic arsenic at different stages in the growing cycle. The good news, according to Pinson, is that the genes responsible for limiting the uptake of both forms of arsenic are already present in U.S. cultivars. But that means that the plants are likely already reducing the arsenic as much as they can, she added, and it will not be easy to find additional genes that would further reduce arsenic in U.S. rice varieties through traditional breeding.

One challenge in tinkering with soil chemistry and plant genetics is blocking arsenic can affect the way a plant takes up other nutrients. There is a balance between this, a tradeoff between the required nutrients and these toxic elements, Parkash said. Its a very complex system.

TThe tradeoff between nutrients and heavy metals plays out beyond the paddy field, and when it comes to setting rules around food, exposure to toxins is not the only consideration.

In recent guidance for arsenic in infant rice cereal, and for lead in baby food more broadly, the FDA notes that strict limits may not be possible for manufacturers. Pinson told Undark that although it is possible to produce rice with relatively low levels of arsenic, supply chain realities make it difficult to achieve low levels in rice-based baby foods, in part because sellers merge grains from multiple truckloads from different farms into single bins, making low-arsenic rice difficult to trace.

The manufacturing process can also increase concentrations in baby food products that make it on the shelf. The February 2021 Economic and Consumer Policy Subcommittee report found that, at least in tests from of one companys products, inorganic arsenic levels were 28 to 93 percent higher in the finished products compared to ingredients. The report points to high levels of arsenic in additives like vitamin mixes and spices as the cause of the spike pre- and post-manufacturing.

There is a balance between this, a tradeoff between the required nutrients and these toxic elements, Parkash said. Its a very complex system.

If food companies cant meet limits on heavy metals in their products, Elisabeth Davis, a spokesperson for the FDA, told Undark that there could be unintended economic consequences for consumers. This includes, she continued, limiting access to foods that have significant nutritional benefits by making them unavailable or unaffordable for many families, or unintentionally increasing the presence of one environmental contaminant when foods are reformulated to reduce the presence of another.

In March 2016, the FDA released a risk assessment that compared economic impacts and the lifetime risk of cancer at various potential guidance levels for arsenic. The risk assessment compared the effect of different parts per billion (ppb) limits which is not a unit of mass, but a description of a ratio. For example, adding about half of a teaspoon of salt to an Olympic-size swimming pool would make it 1 ppb salt. While a 100-ppb limit could lead to anywhere from a 4 to 93 percent loss of rice in the food supply, the FDA calculated that a 75-ppb limit could lead to a 14 to 99 percent loss.

The FDAs risk assessment estimated the average lifetime risk of cancer at different levels of infant rice consumption at various limits of inorganic arsenic. For white rice infant cereal, a limit of 100 parts per billion would reduce the risk of cancer by almost 19 percent, whereas limits of 75 and 50 ppb were calculated to reduce risk by 41 and 79 percent, respectively.

The hazard models the reports authors used are a standard approach, but experts told Undark that the science of calculating health risks around heavy metal contamination is complex. While it is quite straightforward to calculate exposure from water, when it comes to food, White, from the Connecticut Agricultural Experiment Station said: There isnt a formula right now that could be used to actually calculate something like that.

In the end, the FDA recommended inorganic arsenic limits at 100 parts per billion, which it first proposed in draft guidance in April 2016 and finalized in August 2020. This is more lenient than the 10 ppb proposed by national lawmakers in the Baby Food Safety Act, a bill that has stalled in Congress since March 2021. The act would align the inorganic arsenic limits in food with the U.S. Environmental Protection Agencys standard for drinking water, though the 100-ppb limit in food is below the voluntary standards set by the leading international food standards body, the Codex Alimentarius.

Like all of the FDAs guidelines on food limits, 100 parts per billion of arsenic in infant rice cereal is just a recommendation, not a legal requirement. But some evidence suggests the change might be working. The FDA points to a slight downward trend in average concentrations of arsenic in infant rice cereal since it first issued the draft guidance.

However, recent investigations by Consumer Reports and the advocacy group Healthy Babies Bright Futures suggest that at least some baby food in stores across the U.S. contains more than 100 ppb of arsenic four of seven infant rice cereals that were tested exceeded the FDAs limit. The February 2021 report, along with a follow-up report issued that September, showed that several companies set internal limits on arsenic above the FDAs guidance. And some companies found that arsenic levels in infant cereal still surpassed their higher limits.

Undark is a non-profit, editorially independent magazine covering the complicated and often fractious intersection of science and society. If you would like to help support our journalism, please consider making a donation. All proceeds go directly to Undarks editorial fund.

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Baby food manufacturers hold a special position of public trust. Consumers believe that they would not sell unsafe products. Consumers also believe that the federal government would not knowingly permit the sale of unsafe baby food, the report read. Baby food manufacturers and federal regulators had broken the faith.

Despite evidence of arsenic in infant rice cereal above 100 ppb, there was no FDA-mandated recall. Instead, some companies voluntarily pulled products from the shelves. In June 2021, Beech-Nut announced it was leaving the market for rice cereal entirely.

Potential sources of exposure to heavy metals go far beyond the products covered by Closer to Zero. The FDA has no standards for heavy metals in foods beyond the action level for arsenic in infant rice cereal and two draft guidance levels for lead in juice and baby food more broadly. And while processed foods can be systematically tested for heavy metals, Hettiarachchis research has shown that even individual and community gardens can also be contaminated, meaning that the risk of exposure remains even with homemade food.

As for the FDA efforts on reducing heavy metal exposure so far, its good, and I fully support getting closer to zero, Hettiarachchi said. But at the same time, I think we have to do much better.

Colleen Wood is a writer and educator based in New York City. Her work has appeared in The Diplomat, Foreign Policy, New Lines Magazine, and The Washington Post, among other outlets. Find her on Twitter @colleenwood_.

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The Daunting Task of Cutting Heavy Metals from Baby Food - Undark Magazine

Many studies demonstrate that the gut microbiome and metabolome play a critical role in numerous diseases as well as food digestion, immune system regulation, and protection against pathogens. Now, a San Francisco-based biotech company named Envivo Bio and collaborators are advancing the gut microbiome and metabolome field. The company developed a novel device called CapScan, which is the first-of-its-kind to noninvasively and accurately profile the human gut microbiome and metabolome under physiological conditions.

Their findings are detailed in two articles published in Nature and Nature Metabolism.

The first article Human metabolome variation along the upper intestinal tract, is published in Nature Metabolism.

The study revealed noninvasive, in vivo sampling of the human small intestine and ascending colon under physiological conditions showed links between diet, host, and microbial metabolism.

Most processing of the human diet occurs in the small intestine, wrote the researchers.Metabolites in the small intestine originate from host secretions, plus the ingested exposome and microbial transformations. Here we probe the spatiotemporal variation of upper intestinal luminal contents during routine daily digestion in 15 healthy male and female participants. For this, we use a noninvasive, ingestible sampling device to collect and analyze 274 intestinal samples and 60 corresponding stool homogenates by combining five mass spectrometry assays and 16S rRNA sequencing. We identify 1,909 metabolites, including sulfonolipids and fatty acid esters of hydroxy fatty acids (FAHFA) lipids. We observe that stool and intestinal metabolomes differ dramatically.

Our research confirms that, up until now, studies of the gut microbiome have really been studies of the stool microbiome, which missed out on most of the biological activity in our intestinal tract, said Dari Shalon, PhD, founder and CEO of Envivo Bio. By enabling researchers to sample and assess each of the diverse intestinal ecosystems separately and directly for the first time, CapScan opens the door to a new era of microbiome research.

CapScan [Envivo Bio]CapScan is an ingestible collection device that is about the size of a vitamin pill. Each device has a pH-targeted enteric coating, designed to dissolve at a pre-set rate based on the distinct pH levels of the various regions of the human intestines. Once this coating dissolves, CapScans internal bladder opens and draws in luminal content, which is then analyzed outside the body.

Our inability to see and measure the complex ecosystem of the gut has hindered our understanding of the features that make human intestines healthy or diseased, as well as our ability to develop new approaches to treat disease, said Kerwyn Casey (KC) Huang, PhD, professor of bioengineering and of microbiology and immunology, Stanford University, who co-led the study and is senior author on the Nature manuscript. Our research suggests that we may be able to engineer new approaches to this problem.

In the companion Nature article, titled Profiling the human intestinal environment under physiological conditions, researchers from the Chan Zuckerberg Biohub, Max Planck Institute, Pennsylvania State University, Stanford University, University of California, Davis, and two health care systems utilized CapScan to collect 240 intestinal samples from 15 healthy individuals. Each study participant ingested sets of four devices, which were all designed to open at progressively higher pH levels. Once the devices were evacuated, the scientists used multi-omics to analyze the massive sets of microbiome, metabolome, and proteome data collected regionally throughout the gastrointestinal tract.

The researchers found that overall, noninvasive longitudinal profiling of microorganisms, proteins, and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

Taken together, these two studies illustrate the utility and importance of sampling directly from the intestines to enhance our understanding of the relationship between us, our commensal microbes, and the gut metabolome, said Oliver Fiehn, PhD, professor of molecular and cellular biology at the University of California, Davis, and senior author on the Nature Metabolism paper. Routine access to intestinal samples will advance research into human nutrition, and could potentially lead to new therapies for human disease.

Envivo is also collaborating with researchers at Stanford Medicine on a clinical study using CapScan to understand the impact of the gut microbiome on the gut health of mothers and children in low- and middle-income countries with funding provided by the Bill & Melinda Gates Foundation.

As we advance our CapScan technology with improved multi-regional sampling capabilities, we look forward to collaborating with biopharma companies and academic institutions to help improve our understanding of the highly complex gut microbiome and its role in health and disease, added Shalon.

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Ingestible Device Profiles and Peers into the Microbiome and ... - Genetic Engineering & Biotechnology News

Warning: contains spoilers for Sins of Sinister: Dominion!X-Men just officially confirmed the best power set it's possible for any mutant to possess, as fan-favorite hero Rasputin IV is revealed as the masterwork of evil geneticist Mister Sinister. In the recent Sins of Sinister event, fans have seen a potential future where the X-Men's worst selves are unlocked thanks to Sinister's genetic tampering. Under these conditions, Sinister has been free to continue his genetic experiments, creating the ultimate mutant in Rasputin IV - who has subsequently joined X-Men's main canon.

In Kieron Gillen and Alessandro Vitti's Immoral X-Men #3, Sinister reveals that Rasputin IV is his ultimate creation. Throughout the current era of X-Men comics, Sinister has been hard at work creating new 'Chimera' mutants. Chimera are created using cloning technology and the genetic templates of multiple mutants, giving them not just one, but many mutant powers. In Immoral X-Men #2, Sinister confirmed his project was at an end. The most mutant power sets that can possibly be combined is five, and even then, it has to be the right five which can work together on a genetic level. In issue 3, Sinister confirms Rasputin IV is the best possible result - the supreme combination of five powers which can work together without instantly killing the mutant who wields them (the fate of Rasputins I to III)

Related: X-Men's Most Powerful Mutant Names the 1 Person He Can't Beat

Rasputin IV possesses the metal skin and strength of Colossus, the healing of Laura Kinney's Wolverine, the intangibility of Kate Pryde, the force fields of Unus the Untouchable, and the Omega-level telepathy of Kid Omega. Sinister had every mutant genome to pick from, and these five are officially the ultimate power cocktail. While Wolverine, Colossus, and Kate (formerly Kitty) Pryde are household names, Unus is a more obscure villain - first appearing way back in 1964's X-Men #8 - and has an incredibly degree of control over his force fields, which are strong enough to resist the Hulk. Meanwhile, X-Force's Kid Omega, aka Quentin Quire, is as powerful as it's possible for a telepath to be, and has been confirmed as a future Phoenix Force host, on par with Jean Grey. Rasputin IV also wields the Soulsword - a weapon powerful enough to destroy the Silver Surfer, and one which she can use while remaining intangible.

It's worth noting that while Rasputin IV has the best powers possible in a genetic sense, there are more outright powerful mutants. However, these levels of power tend to come with downsides - for example Proteus and Monarch are both capable of altering reality, but this comes with major drawbacks - destroying his body in the process for Proteus, and intense mental instability for Monarch. Likewise, the most outright powerful mutant Legion developed a form of dissociative identity disorder to help differentiate his near-infinite powers. The thing that makes Rasputin IV the triumph of Sinister's genetic engineering is that her powers have no inherent downsides, and they offer wildly versatile combinations.

Rasputin's telepathy and intangibility make her the ultimate stealth agent, while her enhanced strength and healing simultaneously make her a powerhouse brawler. She can shut down Juggernaut with telepathy, stop Rogue laying a finger on her with force fields, and cut through Magik's spells with the Soulsword - all at the same time. Each of her constituent mutants has also found new ways to use their powers that Rasputin IV can apply, from Kate Pryde shorting out electronics on contact to Wolverine achieving bursts of enhanced speed by deliberately over-stressing her muscles. Rasputin IV is not just an Omega-level mutant, but an Omega-level mutant plus four other world-class mutants - all of whose powers she's trained to wield for centuries.

While Sins of Sinister has officially ended, Kieron Gillen, Paco Medina, and Lucas Werneck's Sins of Sinister: Dominion sees Rasputin IV enter Marvel's main reality, meaning the X-Men just got a wildly powerful new member. She may not be able to warp reality, but Rasputin IV officially represents the greatest range of powers any mutant can physically contain, plus Marvel's most powerful mystic weapon. As Fall of X approaches to threaten all of mutantkind, the X-Men may have just encountered the one ally who can save them from extinction.

Sins of Sinister: Dominion is available now from Marvel Comics.

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X-Men Officially Names the Best Powers Any Mutant Can Have - Screen Rant

Marvel is known for putting out hundreds of fantastic characters, but some of the characters that debuted in the '80s are the worst. Whether it be through character design or useless powers, not every character has held up like prominent characters like the Avengers and the X-Men. Some characters were just been bad and will continue to be bad long after their creation.

Though some of these characters, such as the infamous Frog-Man, have been used in more recent comics to try to get them popular again, it doesn't change the fact that they're not the best of characters, to begin with. While they may have a few good qualities about them, their overall design and ineffectiveness against some of the Avengers' most powerful villains and heroes really do not speak highly of their quality as characters.

Related: 10 Public Domain Characters That Exist In DC And Marvel Comics

The second character to use the Gargoyle mantle was Isaac Christians, who allowed his spirit to be placed inside an ancient stone gargoyle by the Six-Fingered Hand to help the villains in exchange for them helping his ailing town. Unfortunately for them, Christians decided to switch sides and help the Defenders, eventually joining their regular roster.

While Christians is a decent enough character, his endearing nature inside a fearsome body is a trope that has been done to death many times previously. With mediocre powers at best and only limited durability, Christians also isn't the greatest in fights against some of Marvel's most powerful villains. Despite all this, he has still made scattered appearances since the '80s, most recently appearing as a member of Iron Man's "Space Friends." Unfortunately, this doesn't really change the fact that he's not a well-made character.

Eugene Patilio, otherwise known as Frog-Man, is certainly in the category of oddball characters Marvel has put out. After discovering a frog suit his father had used for evil, Patilio decided to become a superhero with it, becoming the Fabulous Frog-Man. Sadly, Frog-Man fails to become anything more than a joke character. His victories were by sheer luck, and he is ultimately powerless and useless without the suit he wears. Even with the suit on, the most he can generally do is jump relatively high, and even then, the springs cause him considerable difficulty moving in a straight line, something that only comic book fans know about Frog-Man. It's hard to see this character as anything more than a poorly designed-hero with little use other than a few laughs.

While many different characters have taken up the Jack O'Lantern mantle, the first one to do so was Jason Macendale, Jr. He created the persona to become a mercenary before he became yet another in a long line of characters that have taken up the mantle of Hobgoblin.

Jack O'Lantern, overall, is extremely weak. Much of what he does comes from special effects and weapons, and Macendale's character is just basic, given his CIA-turned-mercenary background. He never even found success as Jack O'Lantern, being one of the weakest villains in Marvel history. Even as the Hobgoblin, Macendale failed to get any traction going for himself, only having moderate success. Overall, he's not much of a character, easily forgettable when compared to better-made ones that are more effective in battle than him, and Jack O'Lantern just becomes another mantle with a revolving door of characters to take it up.

Thomas Fireheart was the result of generations worth of genetic engineering to become the superhuman known as Puma. In his Puma form, Fireheart gained enhanced strength, speed, and senses, and became a mercenary, essentially, working alongside both villains and heroes on multiple different occasions.

Being able to turn into a much stronger, animal-like form is far from making him a great character, however. Puma's moralities have remained so inconsistent over the years that it's hard to see which side he's actually on, whether it be as one of Spider-Man's most powerful animal-themed villains or as his ally. While he can easily put up a good fight in his puma form, his powers have been stripped away from him before, and his reliance on them to be effective in a fight makes him seem even less of a great character than he already was.

Lila Cheney was a mutant with the ability to teleport over large distances. She used this power for her own gain as a thief before going straight after an encounter with the New Mutants. Since then, she's made several small appearances over the decades, even becoming another in a long line of mutants with a connection to Captain Marvel during one such galactic adventure.

Unfortunately, Cheney fails to be an overall great character. Her powers, while incredible, don't work over small distances, leaving her to be nothing more than a transportation service for her allies. She also fails to stand out in any way, aside from her failed early attempt to "sell" Earth to an alien race. Overall, she's a basic character with some potential but has failed to be nothing more than another random mutant sometimes called up to help the X-Men when there's no one else around.

Not much is known about Andromeda's past, other than her claims of her military background in Atlantis and that the villain Attuma is her father, knowledge about Attuma known by comic book fans. Beyond this, she has served Atlantis faithfully and has gone on several adventures on the surface world, most notably with the Defenders. She has even appeared in more recent comics as a member of Namor's Defenders of the Deep.

Andromeda may be useful and a strong fighter overall, but her character design itself is severely lacking. She fails to establish herself in her own way, instead seeking to follow in Namor's footsteps many times. Without an official story about her past, readers have nothing to go on about her background other than what she has claimed, leaving her character weak overall and simply feeling like another prominent Atlantean that stands in the shadow of Namor.

Dennis Dunphy, otherwise known as Demolition Man, or D-Man, first gained his powers through addictive pills supplied by the Power Broker, a villain that comic book fans know much about. After the Power Broker's crimes were revealed, he turned on him and freed himself from the addiction. Following this, he has assisted heroes like Captain America and the Avengers as well as fought them in a few cases.

D-Man problem as a viable character is mostly through his worsening condition. Due to the pills that gave him his powers, he has developed severe physical and mental health problems, making him act irrationally at times. Even with his enhanced strength, he still has yet to prove himself in any real capacity, and in the end, he just seems like another super soldier character created just to increase the size of Marvel's roster further.

The Guthrie family appears to be made entirely of superheroes, as Joshua Guthrie aka Icarus became a mutant just like his older siblings, Sam and Paige, who were a part of the best New Mutants comic issues. Unfortunately, due to a tragic event in which his girlfriend drowned, much of Icarus' time is spent alone brooding over what he has lost.

Overall, the character simply doesn't do much in his few appearances. His backstory, a tragedy that is all too common in superhero origin stories, makes him resent his life and want to die, even driving him to cut off his own wings in an attempt to remove his healing factor along with them. Even though his flight and somewhat hypnotic voice could be a great asset to his friends, he keeps himself out of most fights whenever possible, making him overall a useless character that never does anything.

Right from the start, Dansen Macabre proved to be a character that was not only one of Marvel's least powerful villains but also simply weird rather than great. Her only powers involve being able to hypnotize or kill those that watch her dance. She's used this power to fight heroes like Spider-Man and Captain America.

Despite these incredible powers, Macabre can easily be defeated by those that tune out her dancing. While she does possess some fighting skills, it's not nearly enough to take on most of Marvel's heroes. There's not even much of a backstory for her, as she hasn't appeared very much even after the '80s. She's simply a D-list supervillain that is only a threat to anyone who doesn't already know her powers. Once her powers are found out, she can easily be taken down.

Eshu was once a caveman born 40,000 years ago, much like one of DC Comics' most powerful villains, Vandal Savage. But after being captured by an alien ship, he was able to implant his mind into its computers, giving him superpowers and an extremely long lifespan. Deciding that he wanted to take over the world, he dubbed himself the Master of the World and has gone on to fight heroes, such as Alpha Flight.

Whenever a villain is arrogant enough to dub himself "Master of the World," it's obvious how bad of a character he is. While his powers are strong and he proves himself to be an actual threat many times, there's no denying how similar his background and motivations are to that of Vandal Savage. As such, Eshu comes across as a cheap, flamboyant knockoff that appears every so often to try to take over the world only to be beaten down again by Marvel heroes.

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10 Forgotten Marvel Comics Characters That Debuted In The '80s - Screen Rant