Daily Archives: September 2, 2020

SIOUX FALLS, S.D., Sept. 2, 2020 /PRNewswire/ -- Sanford Health, the largest provider of rural healthcare in the country, today announced it has initiated a Phase 1b trial of SAB-185, a first-of-its-kindhuman polyclonal antibodytherapeutic candidate developed by SAB Biotherapeutics (SAB), that would be used to treat patients with mild to moderate COVID-19 at an early stage of the disease. The trial will enroll a total of 21 adult patients across several clinical sites. Sanford Health is the first site in the country to open the study to patients.

"Today's milestone underscores our relentless commitment to advancing the science of medicine to ensure our patients benefit from new discoveries as quickly as possible," said David A. Pearce, PhD, president of innovation and research at Sanford Health. "Working with SAB Biotherapeutics on this clinical trial gives us an opportunity to deliver on our promise to patients."

"We are eager to participate in this clinical trial to investigate the safety of SAB-185, a human polyclonal antibody therapeutic candidate for COVID-19," said Dr. Susan Hoover, principal investigator and an infectious disease physician at Sanford Health. "Our goal is to advance the science around COVID-19 so physicians can be better prepared to treat this novel coronavirus in the future, especially for our populations most at-risk."

SAB's novel platform, which leverages genetically engineered cattle to produce fully human antibodies, enables scalable and reliable production of specifically targeted, high potency neutralizing antibody products. This approach has expedited the rapid development of this novel immunotherapy for COVID-19, deploying the same natural immune response to fight the disease as recovered patients, but with a much higher concentration of antibodies.

"SAB is pleased to advance SAB-185, one of the leading novel therapeutics for COVID-19, into human trials and leverage the rapid response capabilities of our first-of-its-kind technology during this pandemic, when its needed most," said Eddie Sullivan, founder, president and CEO of SAB Biotherapeutics.

SAB is a Sioux Falls-based biopharmaceutical company advancing a new class of immunotherapies leveraging fully human polyclonal antibodies.Sanford Health is committed to taking research from the bench and bringing promising new treatments to our patients' bedside.New medical discoveries come out of hard work, innovation and research. SAB and Sanford Health are committed to developing and delivering novel solutions to overcome this global pandemic and improve people's lives.

About Sanford HealthSanford Health, one of the largest health systems inthe United States, is dedicated to the integrated delivery of health care, genomic medicine, senior care and services, global clinics, research and affordable insurance. Headquartered inSioux Falls, South Dakota, the organization includes 46 hospitals, 1,400 physicians and more than 200 Good Samaritan Society senior care locations in 26 states and 10 countries. Learn more about Sanford Health's transformative work to improve the human condition atsanfordhealth.orgorSanford Health News.

About SAB BiotherapeuticsSAB Biotherapeutics, Inc. (SAB) is a clinical-stage, biopharmaceutical company advancing a new class of immunotherapies leveraging fully human polyclonal antibodies. Utilizing some of the most complex genetic engineering and antibody science in the world, SAB has developed the only platform that can rapidly produce natural, highly-targeted, high-potency, human polyclonal immunotherapies at commercial scale. The company is advancing programs in autoimmunity, infectious diseases, inflammation and oncology. SAB is rapidly progressing on a new therapeutic for COVID-19, SAB-185, fully human polyclonal antibodies targeted to SARS-CoV-2 without using human donors. For more information visitsabbiotherapeutics.comor follow @SABBantibody on Twitter.

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Sanford Health is first in nation to dose patient with promising novel therapeutic candidate for COVID-19, SAB-185 - PRNewswire

When I asked Facebook about concerns around the ethics of big tech entering the brain-computer interface space, Mr. Chevillet, of Facebook Reality Labs, highlighted the transparency of its brain-reading project. This is why weve talked openly about our B.C.I. research so it can be discussed throughout the neuroethics community as we collectively explore what responsible innovation looks like in this field, he said in an email.

Ed Cutrell, a senior principal researcher at Microsoft, which also has a B.C.I. program, emphasized the importance of treating user data carefully. There needs to be clear sense of where that information goes, he told me. As we are sensing more and more about people, to what extent is that information Im collecting about you yours?

Some find all this talk of ethics and rights, if not irrelevant, then at least premature.

Medical scientists working to help paralyzed patients, for example, are already governed by HIPAA laws, which protect patient privacy. Any new medical technology has to go through the Food and Drug Administration approval process, which includes ethical considerations.

(Ethical quandaries still arise, though, notes Dr. Kirsch. Lets say you want to implant a sensor array in a patient suffering from locked-in syndrome. How do you get consent to conduct surgery that might change the persons life for the better from someone who cant communicate?)

Leigh Hochberg, a professor of engineering at Brown University and part of the BrainGate initiative, sees the companies now piling into the brain-machine space as a boon. The field needs these companies dynamism and their deep pockets, he told me. Discussions about ethics are important, but those discussions should not at any point derail the imperative to provide restorative neurotechnologies to people who could benefit from them, he added.

Ethicists, Dr. Jepsen told me, must also see this: The alternative would be deciding we arent interested in a deeper understanding of how our minds work, curing mental disease, really understanding depression, peering inside people in comas or with Alzheimers, and enhancing our abilities in finding new ways to communicate.

Theres even arguably a national security imperative to plow forward. China has its own version of BrainGate. If American companies dont pioneer this technology, some think, Chinese companies will. People have described this as a brain arms race, Dr. Yuste said.

Not even Dr. Gallant, who first succeeded in translating neural activity into a moving image of what another person was seeing and who was both elated and horrified by the exercise thinks the Luddite approach is an option. The only way out of the technology-driven hole were in is more technology and science, he told me. Thats just a cool fact of life.

Moises Velasquez-Manoff, the author of An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, is a contributing opinion writer.

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The Brain Implants That Could Change Humanity - The New York Times

Johns Hopkins Medicine researchers have added to evidence that a gene responsible for turning off a cells natural suicide signals may also be the culprit in making breast cancer and melanoma cells resistant to therapies that use the immune system to fight cancer. A summary of the research, conducted with mice and human cells, appeared in Cell Reports.When the gene, called BIRC2, is sent into overdrive, it makes too much, or an overexpression, of protein levels. This occurs in about 40% of breast cancers, particularly the more lethal type called triple negative, and it is not known how often the gene is overexpressed in melanomas.

If further studies affirm and refine the new findings, the researchers say, BIRC2 overexpression could be a key marker for immunotherapy resistance, further advancing precision medicine efforts in this area of cancer treatment. A marker of this kind could alert clinicians to the potential need for using drugs that block the genes activity in combination with immunotherapy drugs to form a potent cocktail to kill cancer in some treatment-resistant patients. Cancer cells use many pathways to evade the immune system, so our goal is to find additional drugs in our toolbox to complement the immunotherapy drugs currently in use, says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Genetic Medicine, Pediatrics, Oncology, Medicine, Radiation Oncology and Biological Chemistry at the Johns Hopkins University School of Medicine, and director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering.

Semenza shared the 2019 Nobel Prize in Physiology or Medicine for the discovery of the gene that guides how cells adapt to low oxygen levels, a condition called hypoxia.

In 2018, Semenzas team showed that hypoxia essentially molds cancer cells into survival machines. Hypoxia prompts cancer cells to turn on three genes to help them evade the immune system by inactivating either the identification system or the eat me signal on immune cells. A cell surface protein called CD47 is the only dont eat me signal that blocks killing of cancer cells by immune cells called macrophages. Other cell surface proteins, PDL1 and CD73, block killing of cancer cells by immune cells called T lymphocytes.

These super-survivor cancer cells could explain, in part, Semenza says, why only 20% to 30% of cancer patients respond to drugs that boost the immune systems ability to target cancer cells.

For the current study, building on his basic science discoveries, Semenza and his team sorted through 325 human genes identified by researchers at the Dana Farber Cancer Institute in Boston whose protein products were overexpressed in melanoma cells and linked to processes that help cancer cells evade the immune system.

Semenzas team found that 38 of the genes are influenced by the transcription factor HIF-1, which regulates how cells adapt to hypoxia; among the 38 was BIRC2 (baculoviral IAP repeat-containing 2), already known to prevent cell suicide, or apoptosis, in essence a form of programmed cell death that is a brake on the kind of unchecked cell growth characteristic of cancer.

BIRC2 also blocks cells from secreting proteins that attract immune cells, such as T-cells and natural killer cells.

First, by studying the BIRC2 genome in human breast cancer cells, Semenzas team found that hypoxia proteins HIF1 and HIF2 bind directly to a portion of the BIRC2 gene under low oxygen conditions, identifying a direct mechanism for boosting the BIRC2 genes protein production.

Then, the research team examined how tumors developed in mice when they were injected with human breast cancer or melanoma cells genetically engineered to contain little or no BIRC2 gene expression. In mice injected with cancer cells lacking BIRC2 expression, tumors took longer to form, about three to four weeks, compared with the typical two weeks it takes to form tumors in mice.

The tumors formed by BIRC2-free cancer cells also had up to five times the level of a protein called CXCL9, the substance that attracts immune system T-cells and natural killer cells to the tumor location. The longer the tumor took to form, the more T-cells and natural killer cells were found inside the tumor.

Semenza notes that finding a plentiful number of immune cells within a tumor is a key indicator of immunotherapy success.

Next, to determine whether the immune system was critical to the stalled tumor growth they saw, Semenzas team injected the BIRC2-free melanoma and breast cancer cells into mice bred to have no functioning immune system. They found that tumors grew at the same rate, in about two weeks, as typical tumors. This suggests that the decreased tumor growth rate associated with loss of BIRC2 is dependent on recruiting T-cells and natural killer cells into the tumor, says Semenza.

Finally, Semenza and his team analyzed mice implanted with human breast cancer or melanoma tumors that either produced BIRC2 or were engineered to lack BIRC2. They gave the mice with melanoma tumors two types of immunotherapy FDA-approved for human use, and treated mice with breast tumors with one of the immunotherapy drugs. In both tumor types, the immunotherapy drugs were effective only against the tumors that lacked BIRC2.

Experimental drugs called SMAC mimetics that inactivate BIRC2 and other anti-cell suicide proteins are currently in clinical trials for certain types of cancers, but Semenza says that the drugs have not been very effective when used on their own.

These drugs might be very useful to improve the response to immunotherapy drugs in people with tumors that have high BIRC2 levels, says Semenza.Reference: Samanta D, Huang TYT, Shah R, Yang Y, Pan F, Semenza GL. BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy. Cell Rep. 2020;32(8). doi:10.1016/j.celrep.2020.108073

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cell Suicide Gene Further Linked to Immunotherapy Response - Technology Networks

Johns Hopkins Medicine researchers have added to evidence that a gene responsible for turning off a cell's natural "suicide" signals may also be the culprit in making breast cancer and melanoma cells resistant to therapies that use the immune system to fight cancer. A summary of the research, conducted with mice and human cells, appeared Aug. 25 in Cell Reports.

When the gene, called BIRC2, is sent into overdrive, it makes too much, or an "overexpression," of protein levels. This occurs in about 40% of breast cancers, particularly the more lethal type called triple negative, and it is not known how often the gene is overexpressed in melanomas.

If further studies affirm and refine the new findings, the researchers say, BIRC2 overexpression could be a key marker for immunotherapy resistance, further advancing precision medicine efforts in this area of cancer treatment. A marker of this kind could alert clinicians to the potential need for using drugs that block the gene's activity in combination with immunotherapy drugs to form a potent cocktail to kill cancer in some treatment-resistant patients."Cancer cells use many pathways to evade the immune system, so our goal is to find additional drugs in our toolbox to complement the immunotherapy drugs currently in use," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Genetic Medicine, Pediatrics, Oncology, Medicine, Radiation Oncology and Biological Chemistry at the Johns Hopkins University School of Medicine, and director of the Vascular Program at the Johns Hopkins Institute for Cell Engineering.

Semenza shared the 2019 Nobel Prize in Physiology or Medicine for the discovery of the gene that guides how cells adapt to low oxygen levels, a condition called hypoxia.

In 2018, Semenza's team showed that hypoxia essentially molds cancer cells into survival machines. Hypoxia prompts cancer cells to turn on three genes to help them evade the immune system by inactivating either the identification system or the "eat me" signal on immune cells. A cell surface protein called CD47 is the only "don't eat me" signal that blocks killing of cancer cells by immune cells called macrophages. Other cell surface proteins, PDL1 and CD73, block killing of cancer cells by immune cells called T lymphocytes.

These super-survivor cancer cells could explain, in part, Semenza says, why only 20% to 30% of cancer patients respond to drugs that boost the immune system's ability to target cancer cells.

For the current study, building on his basic science discoveries, Semenza and his team sorted through 325 human genes identified by researchers at the Dana Farber Cancer Institute in Boston whose protein products were overexpressed in melanoma cells and linked to processes that help cancer cells evade the immune system.

Semenza's team found that 38 of the genes are influenced by the transcription factor HIF-1, which regulates how cells adapt to hypoxia; among the 38 was BIRC2 (baculoviral IAP repeat-containing 2), already known to prevent cell "suicide," or apoptosis, in essence a form of programmed cell death that is a brake on the kind of unchecked cell growth characteristic of cancer.

BIRC2 also blocks cells from secreting proteins that attract immune cells, such as T-cells and natural killer cells.

First, by studying the BIRC2 genome in human breast cancer cells, Semenza's team found that hypoxia proteins HIF1 and HIF2 bind directly to a portion of the BIRC2 gene under low oxygen conditions, identifying a direct mechanism for boosting the BIRC2 gene's protein production.

Then, the research team examined how tumors developed in mice when they were injected with human breast cancer or melanoma cells genetically engineered to contain little or no BIRC2 gene expression. In mice injected with cancer cells lacking BIRC2 expression, tumors took longer to form, about three to four weeks, compared with the typical two weeks it takes to form tumors in mice.

The tumors formed by BIRC2-free cancer cells also had up to five times the level of a protein called CXCL9, the substance that attracts immune system T-cells and natural killer cells to the tumor location. The longer the tumor took to form, the more T-cells and natural killer cells were found inside the tumor.

Semenza notes that finding a plentiful number of immune cells within a tumor is a key indicator of immunotherapy success.

Next, to determine whether the immune system was critical to the stalled tumor growth they saw, Semenza's team injected the BIRC2-free melanoma and breast cancer cells into mice bred to have no functioning immune system. They found that tumors grew at the same rate, in about two weeks, as typical tumors. "This suggests that the decreased tumor growth rate associated with loss of BIRC2 is dependent on recruiting T-cells and natural killer cells into the tumor," says Semenza.

Finally, Semenza and his team analyzed mice implanted with human breast cancer or melanoma tumors that either produced BIRC2 or were engineered to lack BIRC2. They gave the mice with melanoma tumors two types of immunotherapy FDA-approved for human use, and treated mice with breast tumors with one of the immunotherapy drugs. In both tumor types, the immunotherapy drugs were effective only against the tumors that lacked BIRC2.

Experimental drugs called SMAC mimetics that inactivate BIRC2 and other anti-cell suicide proteins are currently in clinical trials for certain types of cancers, but Semenza says that the drugs have not been very effective when used on their own.

"These drugs might be very useful to improve the response to immunotherapy drugs in people with tumors that have high BIRC2 levels," says Semenza.

Read more:
Effective cancer immunotherapy further linked to regulating a cell 'suicide' gene - Science Codex

It goes by many names: cultured, in vitro, cell-based, cultivated, lab-grown meat, etc. As the names imply, it is a meat alternative made in a lab via animal cells and a cultured medium, like fetal bovine serum or a proprietary mix of sugars and salts. Several companies around the world are promoting this new technique as a way to cultivate a meat alternative that is supposedly cleaner and safer than traditional meat.

(We are only looking at those products that culture cells taken from animals into a new meat-like formulation. There are many other products that culture plant, fungi, or algal cells into a meat substitute, but we are not reviewing them here.)

29 companies are planning to bring lab-cultured meat to market in the form of chicken, beef, pork, seafood, pet food, and beyond. These companies include Memphis Meats, Aleph Farms, Mosa Meat, Meatable, SuperMeat, and Finless Foods. These companies are backed by huge investments from meat industry corporations (Cargill and Tyson), venture capitalist firms (Blue Yard Capital, Union Square Ventures, S2G Ventures, and Emerald Technology Ventures), and billionaires (such as Bill Gates and Richard Branson).

While the hype is certainly there, is lab-cultured meat actually better? Its proponents tout it as an environmentally responsible, cruelty-free, and antibiotic-free alternative to current meat production. While the goal of producing sustainable meat without killing animals is admirable, lab-cultured meat is in its infancy and the science behind the production methods requires more scrutiny.

Of particular concern is the genetic engineering of cells and their potential cancer-promoting properties. To be able to better assess whether the products are being produced by methods that involve genetic engineering and use genetic constructs (called onco-genes, typically used to make stem cells keep growing; this is not a problem for lab experiments, but could be for food products) that might encourage cancer cells, we need more information on how the cells are engineered and kept growing. Many of the companies are claiming this information is confidential and a business secret. These companies are not yet patenting their production processes wherein this information would be more fully disclosed. Some suggest that the production will follow the FDA cell culture guidelines, but theFDAs cell culture guidelines do not apply to this because theyre not designed for food.

To produce lab-cultured meat, many producers extract animal cells from living animals. This is typically done via biopsy, a painful and uncomfortable procedure that uses large needles. If a company could scale up with this method, it would require a consistent supply of animals from which to acquire cells and innumerable painful extractions. To make the cell-based product more consistent, the producer may biopsy the same animal many times for the cells that growing meat requires.

Growing animal cells (typically muscle cells) also requires a growth medium. When lab-cultured meat production first began, companies depended on fetal bovine serum (FBS) as a growth medium. Producing FBS involves extracting blood from the fetus of a pregnant cow when the cow is slaughtered.

Given its high cost, it appears that FBS is usually only used during small-scale lab trials. Additionally, increasing production capacity using FBS comes with its own set of concerns. Even disregarding the high cost of FBS, non-genetically engineered animal muscle cells only proliferate or increase to a certain degree. In order to overcome this limitation, large companies such as Mosa Meats and Memphis Meats claim theyve found an FBS alternative that does not involve animals along with an effective way to expand production. For Memphis Meats, this process involves the utilization of abioreactor and the creation of immortal cell lines.

Curious about how we make our Memphis Meat? See below! #sogood pic.twitter.com/co5d7OY0bI

Memphis Meats (@MemphisMeats) May 8, 2018

These companies are using a bioreactor essentially a very large vessel for containing biological reactions and processes to implement a scaffold-based system to grow meat, which uses a specific structure for cells to grow on and around. The scaffolding helps the cells differentiate into a specific meat-like formation. Researchers cite using cornstarch fibers, plant skeletons, fungi, and gelatin as common scaffold materials. Instead of animal muscle cell precursors (otherwise known as myosatellites), researchers have been using cultured stem cells. This distinction is important because extracted muscle cells will only proliferate to a certain extent. Companies are trying cultured stem cells as an alternative type of cell(s) that could proliferate exponentially so that they could scale up production, and later differentiate the cells into the various cell types that make up animal meat (muscle, fat, and blood cells) in a bioreactor.

In this process, the stem cells still come from animals or animal embryos, but what differentiates the two methods is that in the scaffold-based system, the cells can be genetically engineered to proliferate indefinitely. These cells are otherwise known as pluripotent (which make many kinds of cells, like stem cells) or totipotent (which make every kind of cell, as do embryos). This would greatly expand a companys capacity to make lab-cultured meat, but the methods by which companies make these cells proliferate come with human health and food safety ramifications.

While the FDA has previously reviewed enzymes, oils, algal, fungal, and bacterial products grown in microorganisms, these new animal cell-cultured products are much more complicated in structure and require a more thorough review. The scale required for making lab-cultured meat feasible for mass consumption will be the largest form of tissue engineering to exist and could introduce new kinds of genetically engineered cells into our diets. Further research will also be needed to conrm or dispel uncertainties over various potential safety issues. Candidate topics for research include the safety of ingesting rapidly growing genetically-modied cell lines, as these lines exhibit the characteristics of a cancerous cell which include overgrowth of cells not attributed to the original characteristics of a population of cultured primary cells. If lab-cultured meat enters the market, there are several human health concerns associated with this new production method, specifically that these genetically-modified cell lines could exhibit the characteristics of a cancerous cell.

While these companies dont disclose much to the public about their processing methods, their public patents reveal the creation of oncogenic, or cancer-causing, cells.A Memphis Meats patent on the creation of modified pluripotent cell lines involves the activation or inactivation of various proteins responsible for tumor suppression. Another patent from JUST Inc. describes the utilization of growth factors as part of its growth medium. This process could promote the development of cancer-like cells in lab-cultured meat products. Additionally, it is possible certain growth factors can be absorbed in the bloodstream after digestion.

If they are using stem cells, cell-based meat companies need to pay attention to the risk of cancer cells emerging in their cultures. A research team from the Harvard Stem Cell Institute (HSCI), Harvard Medical School (HMS), and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard has found that as stem cell lines grow in a lab environment, they often acquire mutations in the TP53 (p53) gene, an important tumor suppressor responsible for controlling cell growth and division. Their research suggests that inexpensive genetic sequencing technologies should be used by cell-based meat companies to screen for mutated cells in stem cell cultures so that these cultures can be excluded.

Cancer-causing additives are prohibited in our food supply under the Delaney Clauses in the 1958 Food Additive Amendments and the 1960 Color Additive Amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA). These new rapidly growing cell lines might be considered color additives if they are being used to produce the color in the meat. The federal statutes regulating meat also prohibit the selling of animals with symptoms of illness, such as cancerous cells in meat. Regardless, all of these new ways of making cells that continue to grow or differentiate should require a safety assessment to determine if they contain cancerous cells before they can be sold.

In describing the scaffolding and growth media being used, lab-cultured meat companies need to be fully transparent about what ingredients theyre using. During the above-mentioned industry nonprofits presentation, the presenter suggested the growth media could be composed of a variety of different ingredients like proteins, amino acids, vitamins, and inorganic salts classified under the GRAS (Generally Recognized As Safe) process that allows companies to do their own testing and not submit to a new FDA food additive review. Since companies are not required to fully disclose the composition of their scaffolding or growth media, potentially exposing consumers to novel proteins and allergens, the new mixture of ingredients should be reviewed under a full FDA supervised food additive review, not GRAS.

Another major issue associated with processing methods using cell lines and/or culture medium is contamination. Unlike animals, cells do not have a fully functioning immune system, so there is a high likelihood of bacterial or fungal growth, mycoplasma, and other human pathogens growing in vats of cells. While lab-cultured meat companies emphasize that this type of meat production would be more sterile than traditional animal agriculture, its unknown how that is true without the use of antibiotics or some other pharmaceutical means of pathogenic control.

Based on commentary from various companies, antibiotic usage across the industry is still very unclear. While the industrys promoters have outlined many uses for antibiotics in lab-grown meat production in preventing contamination, they have not disclosed the amount of antibiotics being used in the various processes. Instead, they suggest that because mass production of lab-grown meat will be done in an industrial rather than lab setting, with bioreactors and tanks, there will be higher safety oversight than in medical labs. It is suggested that the many preventative measures in the industry will maintain a sterile boundary and deter antibiotic use in production. It remains a question of how a food production plant would be more sterile than a medical lab.

Some companies, such as Memphis Meats claim they are genetically engineering cell lines to be antibiotic-resistant, which would suggest they plan on using antibiotics, but dont want their meat cells to be affected. Problems with bacterial and viral contamination plague medical cell culture, so they generally use antimicrobials. Still, any large-scale production that requires antibiotic use even if just for a short-term duration should require such lab-cultured meat undergo even stricter USDA drug residue testing, pathogen testing, and FDA tolerance requirements than conventionally-produced meat. Many other companies claim they dont plan to use antibiotics in expanded production which begs the question, in addition to supposed sterile bioreactors, are they using other undisclosed processes to prevent contamination? For example, Future Meat Technologies describes the use of a special resin to remove toxins.

The companies have also not disclosed plans for how they will dispose of the toxins from bioreactors, scaffolding, and culture media like growth factors/hormones, differentiation factors, often including fetal calf serum or horse serum, and antimicrobials (commonly added to cultured cells to prevent bacterial and fungal contamination, particularly in long-term cultures). In conventionally-produced meat, animals dispose of these toxins in their urine and feces. If companies cant find a way for this meat to dispose of these toxins, they could potentially build up within the meat itself. Given the lack of clarity of these companies and their processes, there must be continuous monitoring of the cell lines and growth media/bioreactor for contaminants and some sort of standardization established across the industry to ensure safety.

The industry is new and the exact production process and inputs needed for large-scale, lab-cultured meat production are unknown (or not being disclosed by the companies). It is the responsibility of both FDA and USDA to ensure that all inputs used in production and the final product are safe for human and animal consumption. These agencies must ensure that lab-cultured meat is labeled appropriately, including if any of the product ingredients are genetically modified or if the ingredients are produced using unmodified cells from animals. These agencies must also ensure that this product doesnt introduce new allergens into the food supply, that any hormones or antibiotics used are not found at unsafe levels in the final product, and that the product doesnt contain any compounds or oncogenic (cancer-causing) cells that have not been approved for use in food.

Lab-cultured meat should not be allowed to use the Generally Recognized As Safe (GRAS) regulatory loophole wherein companies can hire their own experts to evaluate their products, often in secret without any notice to the public or FDA. GRAS is an inappropriate designation because the consensus among knowledgeable experts regarding the safety of lab-cultured meat does not yet exist. Instead, FDA should require that lab-cultured meat products be regulated more thoroughly as food additives. Meat companies should submit complete food additive petitions for each of the novel ingredients used to produce these meats as well as a final food approval petition for the entire product. The production facilities, like all meat processing plants, should then have USDA inspectors on-site monitoring the process and inspecting the meat. The USDA announced in August that it will start the process of developing regulations for these new kinds of meat. Adequate regulation will be necessary to address the concerns raised in this blog.

Overall, due to the novel nature of lab-cultured meat, the lack of transparency from the companies involved, and the myriad potential health risks to consumers, rigorous regulation of this product is vitally important. Join Center for Food Safetys mailing list to protect your right to safe food HERE >>

For those of you interested in eating more plant-based, we highly recommend downloading theFood Monster App with over 15,000 delicious recipes it is the largest plant-based recipe resource to help reduce your environmental footprint, save animals and get healthy! And, while you are at it, we encourage you to also learn about theenvironmentalandhealth benefitsof aplant-based diet.

Here are some great resources to get you started:

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Is Lab-Grown Meat Healthy and Safe to Consume? - One Green Planet

Last week, Gilead Sciences said it would test its COVID-19 drug remdesivir against a related compound in its library called GS-441524 in animal trials, after facing scrutiny over the latter drug, which has been used for years to treat feline infectious peritonitis (FIP) despite not being licensed for that use.

Now, another California biotech, Anivive Lifesciences, is working on a COVID-19 antiviral drug thats inspired by cats, and it has new preclinical research findings to back up the project.

Scientists led by the University of Alberta reported that a drug developed to treat a coronavirus that can cause FIP inhibited the main protease of both SARS-CoV and SARS-CoV-2. That prevented the human coronaviruses from replicating in cell cultures, they reported in the journal Nature Communications.

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Anivive originally licensed the drug, called GC376, from Kansas State University in 2018 and has been working since then to develop it as an antiviral to treat FIP, a progressive disease in cats thats often caused by a coronavirus and is fatal if left untreated. Last month, Anivive said it had started two preclinical studies to determine whether GC376 could also treat COVID-19.

RELATED: COVID-19: New animal data back up Gilead's remdesivir as other treatment candidates emerge

GC376 was designed to inhibit a protease called 3C, which promotes the replication of several coronaviruses that infect animals and people. They include feline coronavirus (FCoV), which usually causes mild symptoms in cats but can lead to FIP.

Two pilot studies of GC376 in pet cats infected with FIP showed that the drug was effective against the disease within two weeks and was well tolerated. Anivive is currently scaling up production of the drug for larger studies in cats.

For the new study, the University of Alberta team tested both GC376 and its parent drug, GC373, for their ability to inhibit the 3C protease. Both drugs blocked viral replication, they reported.

The authors acknowledged that vaccines against COVID-19 are advancing rapidly, but they suggested antiviral drugs are still necessary in the short term. SARS-CoV-2 is a virus with a significant mutation rate. Also, in some patients the virus has persisted longer than 2 months with some possibility of re-infection, they wrote in the study.

M. Joanne Lemieux, Ph.D., professor of structural biology at the University of Alberta, pointed out in an interview with Genetic Engineering & Biotechnology News that GC376 could be advanced rapidly into human trials, given its track record in veterinary medicine.

Because this drug has already been used to treat cats with coronavirus, and its effective with little to no toxicity, its already passed [preclinical] stages, and this allows us to move forward, Lemieux said.

Read more:
Cats point the way to potential COVID-19 remedies - FierceBiotech

Celyad Oncology is at the forefront of cutting-edge immunotherapy and is hopeful of providing a new way forward for patients with relapsed/refractory multiple myeloma. After receiving FDA approval on July 14th to begin Phase I trials, they plan to be in the clinic with their first patient the end of 2020.

The Belgian clinical-stage biotechnology company is focused on the discovery and development of chimeric antigen receptor T cell (CAR-T) therapies for cancer. Celyad Oncology is also developing CYAD-101, an investigational non-gene edited, allogeneic NKG2D-based CAR-T therapy for metastatic colorectal cancer.

The two primary types of cell therapy are autologous and allogeneic. Autologous CAR-T therapy uses the transplantation and genetic editing of a patients own immune cells in a single batch, while an allogeneic transplant uses immune cells from a donor manufactured in large batches. Celyad Oncology is only the fourth company to proceed to Phase I with an allogeneic CAR-T working against a target known as B-cell maturationantigen (BCMA), which is highly expressed in multiple myeloma patients.

The Phase I objectives for CYAD-211 are to establish the viability, effectiveness and further possibilities opened up by the shRNA-based technology. Along with analyzing the merits of targeting BCMA with a CAR-T, Celyad Oncology Chief Executive Officer Filippo Petti shared that the companys first priority is to prove the premise that ShRNA bears out for allogeneic CAR-T.

The first level is to get into the clinic and evaluate the question, is shRNA a novel, non-gene edited allogeneic approach to CAR-T? Where the majority of our peers in the space work on genome using the gene editing technology, if we can show that another non-gene editing technology like ShRNA works, it would just open up the whole field in terms of allogeneic CAR-T. It would demonstrate that we have an unencumbered asset and technology platform for us to create next-generation CAR-T candidates with, Petti said. Well know very quickly, within the first few patients, if we are seeing an absence of graft-versus-host disease, and if ShRNA carries its weight in terms of being an allogeneic technology.

He expects to have a sense of how competitive the data is in terms of both safety and clinical efficacy by end of year 2021.

Dr. Laurence Cooper, Chief Executive Officer (CEO) of Ziopharm Oncology, who is also a veteran innovator in pairing genetic engineering with immunotherapies, explained that Graft-versus-Host Disease (GvHD) is one of biggest challenges facing companies who take the allogeneic approach.

When you put in third party cells, those cells get really confused right off the bat because now theyre somewhere new, and all of a sudden they perceive the patient as the threat. This can result in Graft-versus-Host Disease, an autoimmune disease triggered by the native biology in the T cell through its T cell receptor, Cooper said. The engineering that youre talking about is to eliminate that threat. Some cut out the genetic material coding for the endogenous T cell receptor so that now a T cell can go into another person, and it cant perceive the threat anymore because its lost its antennae. Another way is to prevent expression of the T cell receptor. Now the T cell can do something useful if you put in a CAR, it can go off and targetBCMA.

Frdric F. Lehmann, Head of the Oncology Franchise at Celyad Oncology, explained how the shRNA-based therapy is engineered to reign in the cells new rampant disregard for threat, and lessen the chances of an autoimmune response.

One of the innovations for CYAD-211 is incorporating in the vector a short hairpin RNA (shRNA) targeting the CD3 subunit of the T cell Receptor (TCR). This effectively downregulates the surface expression of the TCR thereby inhibiting the signaling that would lead to Graft-versus-Host Disease, Lehmann said.

A notable drawback with the autologous approach to CAR-T therapy is that it is costly and time-consuming. Petti explained how CYAD-211 not only has the potential to improve efficacy, but also make the treatment process more scalable and therefore economically expedient.

When it comes to commercialization, because we use an all-in-one-vector approach, we benefit from less manipulations during manufacturing, allowing us to enrich for the engineered cells we want, which eventually could help during potential commercialization of a product thats streamlined, Petti said.

He added that the all-in-one vector approach increases efficiency because, as opposed to the case with the gene editing process, they are able to accomplish everything in a single step.

Long term, Cooper is excited about the possibility that, whether autologous or allogeneic, immunotherapy may one day replace bone marrow transplants, or even chemotherapy, but emphasized that it must be made accessible.

If these immunotherapies can be advanced really to replace chemotherapy, not to replace transplantation for liquid tumors, but to replace chemotherapy, which is a huge goal if you can get it to do that, you have to bring the costs down to make it available for the masses, inside first world economies as well as less privileged societies, Cooper said.

In 2013, the overall five-year survival rate for multiple myeloma stood at 49.6%. Relapsed/refractory patients for whom currently available treatments have failed, are the intended beneficiaries of much of the biotechnology work being done in this area. And impressive steps have recently been made.

GlaxoSmithKlines BLENREP (BelantamabMafodotin) is the first in its class to work against BCMA, while Janssen Biotechs (Johnson & Johnson) DARZALEX (Daratumumab) is the first human Anti-CD38 monoclonal antibody in the space. After their 2019 acquisition of Celgene Corp., Bristol-Myers Squibb gained Revlimid (Lenalidomide), a hematology drug approved for multiple myeloma, and Amgen and Takeda have popular proteasome inhibitors on the market.

With Celyad Oncology moving the needle forward once again, the future looks a little brighter for multiple myeloma patients.

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Celyad's High Hopes for a Path Forward in Cancer Immunotherapy with CYAD-211 - BioSpace

Efforts to use regenerative medicinewhich seeks to address ailments as diverse as birth defects, traumatic injury, aging, degenerative disease, and the disorganized growth of cancerwould be greatly aided by solving one fundamental puzzle: How do cellular collectives orchestrate the building of complex, three-dimensional structures?

While genomes predictably encode the proteins present in cells, a simple molecular parts list does not tell us enough about the anatomical layout or regenerative potential of the body that the cells will work to construct. Genomes are not a blueprint for anatomy, and genome editing is fundamentally limited by the fact that its very hard to infer which genes to tweak, and how, to achieve desired complex anatomical outcomes. Similarly, stem cells generate the building blocks of organs, but the ability to organize specific cell types into a working human hand or eye has been and will be beyond the grasp of direct manipulation for a very long time.

But researchers working in the fields of synthetic morphology and regenerative biophysics are beginning to understand the rules governing the plasticity of organ growth and repair. Rather than micromanaging tasks that are too complex to implement directly at the cellular or molecular level, what if we solved the mystery of how groups of cells cooperate to construct specific multicellular bodies during embryogenesis and regeneration? Perhaps then we could figure out how to motivate cell collectives to build whatever anatomical features we want.

New approaches now allow us to target the processes that implement anatomical decision-making without genetic engineering. In January, using such tools, crafted in my lab at Tufts Universitys Allen Discovery Center and by computer scientists in Josh Bongards lab at the University of Vermont, we were able to create novel living machines, artificial bodies with morphologies and behaviors completely different from the default anatomy of the frog species (Xenopus laevis) whose cells we used. These cells rebooted their multicellularity into a new form, without genomic changes. This represents an extremely exciting sandbox in which bioengineers can play, with the aim of decoding the logic of anatomical and behavioral control, as well as understanding the plasticity of cells and the relationship of genomes to anatomies.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking.

Deciphering how an organism puts itself together is truly an interdisciplinary undertaking. Resolving the whole picture will involve understanding not only the mechanisms by which cells operate, but also elucidating the computations that cells and groups of cells carry out to orchestrate tissue and organ construction on a whole-body scale. The next generation of advances in this area of research will emerge from the flow of ideas between computer scientists and biologists. Unlocking the full potential of regenerative medicine will require biology to take the journey computer science has already taken, from focusing on the hardwarethe proteins and biochemical pathways that carry out cellular operationsto the physiological software that enables networks of cells to acquire, store, and act on information about organ and indeed whole-body geometry.

In the computer world, this transition from rewiring hardware to reprogramming the information flow by changing the inputs gave rise to the information technology revolution. This shift of perspective could transform biology, allowing scientists to achieve the still-futuristic visions of regenerative medicine. An understanding of how independent, competent agents such as cells cooperate and compete toward robust outcomes, despite noise and changing environmental conditions, would also inform engineering. Swarm robotics, Internet of Things, and even the development of general artificial intelligence will all be enriched by the ability to read out and set the anatomical states toward which cell collectives build, because they share a fundamental underlying problem: how to control the emergent outcomes of systems composed of many interacting units or individuals.

Many types of embryos can regenerate entirely if cut in half, and some species are proficient regenerators as adults. Axolotls (Ambystoma mexicanum) regenerate their limbs, eyes, spinal cords, jaws, and portions of the brain throughout life. Planarian flatworms (class Turbellaria), meanwhile, can regrow absolutely any part of their body; when the animal is cut into pieces, each piece knows exactly whats missing and regenerates to be a perfect, tiny worm.

The remarkable thing is not simply that growth begins after wounding and that various cell types are generated, but that these bodies will grow and remodel until a correct anatomy is complete, and then they stop. How does the system identify the correct target morphology, orchestrate individual cell behaviors to get there, and determine when the job is done? How does it communicate this information to control underlying cell activities?

Several years ago, my lab found that Xenopus tadpoles with their facial organs experimentally mixed up into incorrect positions still have largely normal faces once theyve matured, as the organs move and remodel through unnatural paths. Last year, a colleague at Tufts came to a similar conclusion: the Xenopus genome does not encode a hardwired set of instructions for the movements of different organs during metamorphosis from tadpole to frog, but rather encodes molecular hardware that executes a kind of error minimization loop, comparing the current anatomy to the target frog morphology and working to progressively reduce the difference between them. Once a rough spatial specification of the layout is achieved, that triggers the cessation of further remodeling.

The deep puzzle of how competent agents such as cells work together to pursue goals such as building, remodeling, or repairing a complex organ to a predetermined spec is well illustrated by planaria. Despite having a mechanistic understanding of stem cell specification pathways and axial chemical gradients, scientists really dont know what determines the intricate shape and structure of the flatworms head. It is also unknown how planaria perfectly regenerate the same anatomy, even as their genomes have accrued mutations over eons of somatic inheritance. Because some species of planaria reproduce by fission and regeneration, any mutation that doesnt kill the neoblastthe adult stem cell that gives rise to cells that regenerate new tissueis propagated to the next generation. The worms incredibly messy genome shows evidence of this process, and cells in an individual planarian can have different numbers of chromosomes. Still, fragmented planaria regenerate their body shape with nearly 100 percent anatomical fidelity.

Permanent editingof the encoded target morphology without genomic editing reveals a new kind of epigenetics.

So how do cell groups encode the patterns they build, and how do they know to stop once a target anatomy is achieved? What would happen, for example, if neoblasts from a planarian species with a flat head were transplanted into a worm of a species with a round or triangular head that had the head amputated? Which shape would result from this heterogeneous mixture? To date, none of the high-resolution molecular genetic studies of planaria give any prediction for the results of this experiment, because so far they have all focused on the cellular hardware, not on the logic of the softwareimplemented by chemical, mechanical, and electrical signaling among cellsthat controls large-scale outcomes and enables remodeling to stop when a specific morphology has been achieved.

Understanding how cells and tissues make real-time anatomical decisions is central not only to achieving regenerative outcomes too complex for us to manage directly, but also to solving problems such as cancer. While the view of cancer as a genetic disorder still largely drives clinical approaches, recent literature supports a view of cancer as cells simply not being able to receive the physiological signals that maintain the normally tight controls of anatomical homeostasis. Cut off from these patterning cues, individual cells revert to their ancient unicellular lifestyle and treat the rest of the body as external environment, often to ruinous effect. If we understand the mechanisms that scale single-cell homeostatic setpoints into tissue- and organ-level anatomical goal states and the conditions under which the anatomical error reduction control loop breaks down, we may be able to provide stimuli to gain control of rogue cancer cells without either gene therapy or chemotherapy.

During morphogenesis, cells cooperate to reliably build anatomical structures. Many living systems remodel and regenerate tissues or organs despite considerable damagethat is, they progressively reduce deviations from specific target morphologies, and halt growth and remodeling when those morphologies are achieved. Evolution exploits three modalities to achieve such anatomical homeostasis: biochemical gradients, bioelectric circuits, and biophysical forces. These interact to enable the same large-scale form to arise despite significant perturbations.

N.R. FULLER, SAYO-ART, LLC

BIOCHEMICAL GRADIENTS

The best-known modality concerns diffusible intracellular and extracellular signaling molecules. Gene-regulatory circuits and gradients of biochemicals control cell proliferation, differentiation, and migration.

BIOELECTRIC CIRCUITS

The movement of ions across cell membranes, especially via voltage-gated ion channels and gap junctions, can establish bioelectric circuits that control large-scale resting potential patterns within and among groups of cells. These bioelectric patterns implement long-range coordination, feedback, and memory dynamics across cell fields. They underlie modular morphogenetic decision-making about organ shape and spatial layout by regulating the dynamic redistribution of morphogens and the expression of genes.

BIOMECHANICAL FORCES

Cytoskeletal, adhesion, and motor proteins inside and between cells generate physical forces that in turn control cell behavior. These forces result in large-scale strain fields, which enable cell sheets to move and deform as a coherent unit, and thus execute the folds and bends that shape complex organs.

The software of life, which exploits the laws of physics and computation, is enabled by chemical, mechanical, and electrical signaling across cellular networks. While the chemical and mechanical mechanisms of morphogenesis have long been appreciated by molecular and cell biologists, the role of electrical signaling has largely been overlooked. But the same reprogrammability of neural circuits in the brain that supports learning, memory, and behavioral plasticity applies to all cells, not just neurons. Indeed, bacterial colonies can communicate via ionic currents, with recent research revealing brain-like dynamics in which information is propagated across and stored in a kind of proto-body formed by bacterial biofilms. So it should really come as no surprise that bioelectric signaling is a highly tractable component of morphological outcomes in multicellular organisms.

A few years ago, we studied the electrical dynamics that normally set the size and borders of the nascent Xenopus brain, and built a computer model of this process to shed light on how a range of various brain defects arise from disruptions to this bioelectric signaling. Our model suggested that specific modifications with mRNA or small molecules could restore the endogenous bioelectric patterns back to their correct layout. By using our computational platform to select drugs to open existing ion channels in nascent neural tissue or even a remote body tissue, we were able to prevent and even reverse brain defects caused not only by chemical teratogenscompounds that disrupt embryonic developmentbut by mutations in key neurogenesis genes.

Similarly, we used optogenetics to stimulate electrical activity in various somatic cell types totrigger regeneration of an entire tadpole tailan appendage with spinal cord, muscle, and peripheral innervationand to normalize the behavior of cancer cells in tadpoles strongly expressing human oncogenes such as KRAS mutations. We used a similar approach to trigger posterior regions, such as the gut, to build an entire frog eye. In both the eye and tail cases, the information on how exactly to build these complex structures, and where all the cells should go, did not have to be specified by the experimenter; rather, they arose from the cells themselves. Such findings reveal how ion channel mutations result in numerous human developmental channelopathies, and provide a roadmap for how they may be treated by altering the bioelectric map that tells cells what to build.

We also recently found a striking example of such reprogrammable bioelectrical software in control of regeneration in planaria. In 2011, we discovered that an endogenous electric circuit establishes a pattern of depolarization and hyperpolarization in planarian fragments that regulate the orientation of the anterior-posterior axis to be rebuilt. Last year, we discovered that this circuit controls the gene expressionneeded to build a head or tail within six hours of amputation, and by using molecules that make cell membranes permeable to certain ions to depolarize or hyperpolarize cells, we induced fragments of such worms to give rise to a symmetrical two-headed form, despite their wildtype genomes. Even more shockingly, the worms continued to generate two-headed progeny in additional rounds of cutting with no further manipulation. In further experiments, we demonstrated that briefly reducing gap junction-mediated connectivity between adjacent cells in the bioelectric network that guides regeneration led worms to regenerate head and brain shapes appropriate to other worm species whose lineages split more than 100 million years ago.

My group has developed the use of voltage-sensitive dyes to visualize the bioelectric pattern memory that guides gene expression and cell behavior toward morphogenetic outcomes. Meanwhile, my Allen Center colleagues are using synthetic artificial electric tissues made of human cells and computer models of ion channel activity to understand how electrical dynamics across groups of non-neural cells can set up the voltage patterns that control downstream gene expression, distribution of morphogen molecules, and cell behaviors to orchestrate morphogenesis.

The emerging picture in this field is that anatomical software is highly modulara key property that computer scientists exploit as subroutines and that most likely contributes in large part to biological evolvability and evolutionary plasticity. A simple bioelectric state, whether produced endogenously during development or induced by an experimenter, triggers very complex redistributions of morphogens and gene expression cascades that are needed to build various anatomies. The information stored in the bodys bioelectric circuitscan be permanently rewritten once we understand the dynamics of the biophysical circuits that make the critical morphological decisions. This permanent editing of the encoded target morphology without genomic editing reveals a new kind of epigenetics, information that is stored in a medium other than DNA sequences and chromatin.

Recent work from our group and others has demonstrated that anatomical pattern memories can be rewritten by physiological stimuli and maintained indefinitely without genomic editing. For example, the bioelectric circuit that normally determines head number and location in regenerating planaria can be triggered by brief alterations of ion channel or gap junction activity to alter the animals body plan. Due to the circuits pattern memory, the animals remain in this altered state indefinitely without further stimulation, despite their wildtype genomes. In other words, the pattern to which the cells build after damage can be changed, leading to a target morphology distinct from the genetic default.

N.R. FULLER, SAYO-ART, LLC

First, we soaked a planarian in voltage-sensitive fluorescent dye to observe the bioelectrical pattern across the entire tissue. We then cut the animal to see how this pattern changes in each fragment as it begins to regenerate.

We then applied drugs or used RNA interference to target ion channels or gap junctions in individual cells and thus change the pattern of depolarization/hyperpolarization and cellular connectivity across the whole fragment.

As a result of the disruption of the bodys bioelectric circuits, the planarian regrows with two heads instead of one, or none at all.

When we re-cut the two-headed planarian in plain water, long after the initial drug has left the tissue, the new anatomy persists in subsequent rounds of regeneration.

Cells can clearly build structures that are different from their genomic-default anatomical outcomes. But are cells universal constructors? Could they make anything if only we knew how to motivate them to do it?

The most recent advances in the new field at the intersection of developmental biology and computer science are driven by synthetic living machines known as biobots. Built from multiple interacting cell populations, these engineered machines have applications in disease modeling and drug development, and as sensors that detect and respond to biological signals. We recently tested the plasticity of cells by evolving in silico designs with specific movement and behavior capabilities and used this information to sculpt self-organized growth of aggregated Xenopus skin and muscle cells. In a novel environmentin vitro, as opposed to inside a frog embryoswarms of genetically normal cells were able to reimagine their multicellular form. With minimal sculpting post self-assembly, these cells form Xenobots with structures, movements, and other behaviors quite different from what might be expected if one simply sequenced their genome and identified them as wildtype X. laevis.

These living creations are a powerful platform to assess and model the computations that these cell swarms use to determine what to build. Such insights will help us to understand evolvability of body forms, robustness, and the true relationship between genomes and anatomy, greatly potentiating the impact of genome editing tools and making genomics more predictive for large-scale phenotypes. Moreover, testing regimes of biochemical, biomechanical, and bioelectrical stimuli in these biobots will enable the discovery of optimal stimuli for use in regenerative therapies and bioengineered organ construction. Finally, learning to program highly competent individual builders (cells) toward group-level, goal-driven behaviors (complex anatomies) will significantly advance swarm robotics and help avoid catastrophes of unintended consequences during the inevitable deployment of large numbers of artificial agents with complex behaviors.

Understanding how cells and tissues make real-time anatomical decisions is central to achieving regenerative outcomes too complex for us to manage directly.

The emerging field ofsynthetic morphology emphasizes a conceptual point that has been embraced by computer scientists but thus far resisted by biologists: the hardware-software distinction. In the 1940s, to change a computers behavior, the operator had to literally move wires aroundin other words, she had to directly alter the hardware. The information technology revolution resulted from the realization that certain kinds of hardware are reprogrammable: drastic changes in function could be made at the software level, by changing inputs, not the hardware itself.

In molecular biomedicine, we are still focused largely on manipulating the cellular hardwarethe proteins that each cell can exploit. But evolution has ensured that cellular collectives use this versatile machinery to process information flexibly and implement a wide range of large-scale body shape outcomes. This is biologys software: the memory, plasticity, and reprogrammability of morphogenetic control networks.

The coming decades will be an extremely exciting time for multidisciplinary efforts in developmental physiology, robotics, and basal cognition to understand how individual cells merge together into a collective with global goals not belonging to any individual cell. This will drive the creation of new artificial intelligence platforms based not on copying brain architectures, but on the multiscale problem-solving capacities of cells and tissues. Conversely, the insights of cognitive neurobiology and computer science will give us a completely new window on the information processing and decision-making dynamics in cellular collectives that can very effectively be targeted for transformative regenerative therapies of complex organs.

Michael Levinis the director of the Allen Discovery Center at Tufts University and Associate Faculty at Harvard Universitys Wyss Institute. Email him atmichael.levin@tufts.edu. M.L. thanks Allen Center Deputy DirectorJoshua Finkelsteinfor suggestions on the drafts of this story.

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How Groups of Cells Cooperate to Build Organs and Organisms - The Scientist

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualised gene-targeted fixes

Tom Hanks and his wife, Rita Wilson, were among the earliest celebrities to catch the novel coronavirus. In an interview at the beginning of July, Hanks described how differently COVID-19 had affected each of them in March.

My wife lost her sense of taste and smell, she had severe nausea, she had a much higher fever than I did. I just had crippling body aches, he said. I was very fatigued all the time and I couldnt concentrate on anything for more than about 12 minutes.

Why does COVID-19 present such different symptoms or none at all in different people?

Preexisting conditions can only be part of the story. Hanks is over 60 and is a Type 2 diabetic, putting him in a high-risk group. Nevertheless, he survived his brush with the virus with no pneumonia and apparently without any long-lasting effects. Knowing what causes variation in different patients could help physicians tailor their treatments to individual patients an approach known as precision medicine.

In recent years, a gene-centric approach to precision medicine has been promoted as the future of medicine. It underlies the massive effort funded by the US National Institutes of Health to collect over a million DNA samples under the All of Us initiative that began in 2015.

But the imagined future did not include COVID-19. In the rush to find a COVID-19 vaccine and effective therapies, precision medicine has been insignificant. Why is this? And what are its potential contributions?

We are a physician geneticist and a philosopher of science who began a discussion about the promise and potential pitfalls of precision medicine before the arrival of COVID-19. If precision medicine is the future of medicine, then its application to pandemics generally, and COVID-19 in particular, may yet prove to be highly significant. But its role so far has been limited. Precision medicine must consider more than just genetics. It requires an integrative omic approach that must collect information from multiple sources beyond just genes and at scales ranging from molecules to society.

From genetics to microbes

Inherited diseases such as sickle cell anemia and Tay-Sachs disease follow a predictable pattern. But such direct genetic causes are perhaps the exception rather than the rule when it comes to health outcomes. Some heritable conditions for instance, psoriasis or the many forms of cancer depend on complex combinations of genes, environmental and social factors whose individual contributions to the disease are difficult to isolate. At best, the presence of certain genes constitutes a risk factor in a population but does not fully determine the outcome for an individual person carrying those genes.

The situation becomes yet more complicated for infectious diseases.

Viruses and bacteria have their own genomes that interact in complex ways with the cells in the people they infect. The genome of SARS-CoV-2 underlying COVID-19 has been extensively sequenced. Its mutations are identified and traced worldwide, helping epidemiologists understand the spread of the virus. However, the interactions between SARS-CoV-2 RNA and human DNA, and the effect on people of the viruss mutations, remain unknown.

The importance of multi-scale data

Tom Hanks and his wife caught the virus and recovered in a matter of weeks. Presumably each was infected over the course of a few minutes of exposure to another infected person, involving cellular mechanisms that operate on a timescale of milliseconds.

But the drama of their illness, and that of the many victims with far worse outcomes, is taking place in the context of a global pandemic that has already lasted months and may continue for years. People will need to adopt changes in their behavior for weeks or months at a time.

What should a precision medicine approach be in a pandemic? The gene-centric vision of precision medicine encourages people to expect individualised gene-targeted fixes. But, genes, behavior and social groups interact over multiple timescales.

To capture all the data needed for such an approach is beyond possibility in the current crisis. A nuanced approach to the COVID-19 pandemic will depend heavily on imprecise population level public health interventions: mask-wearing, social distancing and working from home. Nevertheless, there is an opportunity to begin gathering the kinds of data that would allow for a more comprehensive precision medicine approach one that is fully aware of the complex interactions between genomes and social behavior.

How to use precision medicine to understand COVID-19

With unlimited resources, a precision medicine approach would begin by analyzing the genomes of a large group of people already known to be exposed to SARS-CoV-2 yet asymptomatic, along with a similar-sized group with identified risk factors who are dying from the disease or are severely ill.

An early study of this kind by Precisionlife Ltd data mined genetic samples of 976 known COVID-19 cases. Of these, 68 high-risk genes were identified as risk factors for poor COVID-19 outcomes, with 17 of them deemed likely to be good targets for drug developments. But, as with all such statistical approaches, the full spectrum of causes underlying their association with the disease is not something the analysis provides. Other studies of this kind are appearing with increasing frequency, but there is no certainty in such fast-moving areas of science. Disentangling all the relevant factors is a process that will take months to years.

To date, precision medicine has proven better suited to inherited diseases and to diseases such as cancer, involving mutations acquired during a persons lifetime, than to infectious diseases. There are examples where susceptibility to infection can be caused by malfunction of unique genes such as the family of inherited immune disorders known as agammaglobulinemia, but these are few and far between.

Many physicians assume that most diseases involve multiple genes and are thus not amenable to a precision approach. In the absence of the kind of information needed for a multi-omic approach, there is a clear challenge and opportunity for precision medicine here: If it is to be the future of medicine, in order to complement and expand our existing knowledge and approaches, it needs to shift from its gene-centric origins toward a broader view that includes variables like proteins and metabolites. It must consider the relationships between genes and their physical manifestations on scales that range from days to decades, and from molecules to the global society.

Colin Allen, Distinguished Professor of History & Philosophy of Science, University of Pittsburgh and David Finegold, Professor, Department of Human Genetics, Pitt Public Health, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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How to use precision medicine to personalise COVID-19 treatment according to the patient's genes - Down To Earth Magazine

Before bacteria colonize a tissue in the human body, such as the intestine, they have to attach. Not only that, they have to achieve firm adhesion under hydrodynamic flow. New research reports a molecular mechanism behind an ultrastable protein complex responsible for resisting shear forces and adhering bacteria to cellulose fibers in the human gut. The results explain how gut microbes regulate cell adhesion strength at high shear stress through intricate molecular mechanisms including dual-binding modes, mechanical allostery, and catch bonds.

The researchers used single-molecule force spectroscopy (SMFS), single-molecule FRET (smFRET), and molecular dynamics (MD) simulations to uncover that two different binding modes allow bacteria to withstand the shear forces in the body. The findings are published in Nature Communications in the paper titled, High force catch bond mechanism of bacterial adhesion in the human gut.

Cellulose is a major building block of plant cell walls, consisting of molecules linked together into solid fibers. For humans, cellulose is indigestible, and the majority of gut bacteria lack the enzymes required to break down cellulose.

However, recently genetic material from the cellulose-degrading bacterium R. champanellensis was detected in human gut samples. Bacterial colonization of the intestine is essential for human physiology, and understanding how gut bacteria adhere to cellulose broadens our knowledge of the microbiome and its relationship to human health.

The bacterium under investigation uses an intricate network of scaffold proteins and enzymes on the outer cell wall, referred to as a cellulosome network, to attach to and degrade cellulose fibers. These cellulosome networks are held together by families of interacting proteins.

Of particular interest is the cohesin-dockerin interaction responsible for anchoring the cellulosome network to the cell wall. This interaction needs to withstand shear forces in the body to adhere to fiber. This vital feature motivated the researchers to investigate in more detail how the anchoring complex responds to mechanical forces.

By using a combination of single-molecule atomic force microscopy, single-molecule fluorescence, and molecular dynamics simulations, Michael Nash, PhD, assistant professor with joint appointments at the University of Basel, department of chemistry, and at ETH Zurich, department of biosystems science & engineering, along with collaborators from LMU Munich and Auburn University, studied how the complex resists external force.

Two binding modes allow bacteria to stick to surfaces under shear flow

They were able to show that the complex exhibits a rare behavior called dual binding mode, where the proteins form a complex in two distinct ways. The researchers found that the two binding modes have very different mechanical properties, with one breaking at low forces of around 200 piconewtons and the other exhibiting a much higher stability breaking only at 600 piconewtons of force.

Further analysis showed that the protein complex displays a behavior called a catch bond, meaning that the protein interaction becomes stronger as force is ramped up. The dynamics of this interaction are believed to allow the bacteria to adhere to cellulose under shear stress and release the complex in response to new substrates or to explore new environments.

We clearly observe the dual binding modes, but can only speculate on their biological significance. We think the bacteria might control the binding mode preference by modifying the proteins. This would allow switching from a low to high adhesion state depending on the environment, Nash explained.

By shedding light on this natural adhesion mechanism, these findings set the stage for the development of artificial molecular mechanisms that exhibit similar behavior but bind to disease targets. Such materials could have applications in bio-based medical superglues or shear-enhanced binding of therapeutic nanoparticles inside the body. For now, we are excited to return to the laboratory and see what sticks, said Nash.

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Bacterial Superglue Allows Adhesion to the Gut - Genetic Engineering & Biotechnology News