thescientist--2020-11-16--The MSC: Regeneration Orchestrator

The MSC: Regeneration Orchestrator

The mysteries of a salamander regenerating its tail or a sea cucumber mending its organs have fascinated humans and perplexed scientists for centuries .
The idea that the human body holds similar mechanisms to heal and repair itself is tantalizing and not altogether impossible .
There are powerful cells called mesenchymal stem cells situated on the 50,000–100,000 miles of blood vessels in the human body .
These cells carry the ability to initiate signaling cascades that drive tissue repair and regeneration .
In the mid-1960s , Marshall Urist , an orthopedic surgeon at the University of California Center for Health @ @ @ @ @ @ @ the mineral calcium phosphate from pieces of bone .
Urist took the remaining demineralized bone components and placed them into the muscle of an adult mouse and made the surprising discovery that bone could subsequently form in muscle tissue.1 In the late 1960s , Arnold Caplan , now professor of biology and director of the Skeletal Research Center at Case Western Reserve University , was perfecting a cell culture medium cocktail that converted cells he isolated from the presumptive wings and legs of chicken embryos into cartilage , bone , or muscle .
@ @ @ @ @ @ @ signals that differentiated these cells into specialized tissue lineages .
When Caplan learned of Ursit ’ s results , he was intrigued .
“ I realized that there were stem cells—cells that could respond to powerful inductive molecules that must exist in the adult tissue , ” said Caplan .
“ And so , coming from an orthopedic background , I knew that there were magic cells , magic elixirs , in bone marrow.
” Bone marrow has been associated with orthopedic healing since the days of Aristotle , and several studies in @ @ @ @ @ @ @ progenitor cells .
Together with one of his post-doctoral researchers , Stephen Haynesworth , Caplan began purifying cells from human bone marrow in a search for cell types that make bone , relying on the same medium cocktail he perfected for embryonic chicken cells.2 “ That magic medium was the whole trick to the entire mesenchymal stem cell technology , ” said Caplan .
“ In that medium , the cells from bone marrow , which are very rare—one in 100,000 , one in a million—stuck to the Petri dish and divided like @ @ @ @ @ @ @ that they could manipulate the adhered bone marrow cells to differentiate into muscle , cartilage , bone , or fat on tissue culture dishes .
This ability to readily form a variety of cell types from the middle or mesenchymal layer of the body suggested a new type of adult stem cell , leading Caplan to coin the term “ mesenchymal stem cell ( MSC ) .
” Colorized scanning electron micrograph ( SEM ) of a human mesenchymal stem cell ( MSC ) “ It turns out that that was a mistake @ @ @ @ @ @ @ the time believed that cells behaved the same in tissue culture as they did within the body .
“ MSCs inside your body never differentiate the cartilage , never differentiate the bone , never differentiate the fat .
So , in your body , these cells are not stem cells , ” said Caplan .
Instead , they are much more .
In the body , MSCs play an important role in maintaining stem or progenitor cell niches and homeostasis .
They arise from perivascular cells called pericytes that reside on the surface @ @ @ @ @ @ @ a filter between blood vessels and tissues .
If a blood vessel in any tissue becomes damaged , pericytes fall off the vessels and differentiate into MSCs that then orchestrate the formation of new vessels and tissues by recruiting and activating adult stem cells or progenitor cells that are already present in the tissue.3,4 “ If you break a bone , there is a cell in your bone that is already there to make new bone .
What the MSC does is pause that cell , give it a molecule to make it @ @ @ @ @ @ @ the new bone .
The MSC does n't make the new bone .
The MSC is the instructor , the manager of the regeneration of every tissue , ” said Caplan .
MSCs also act as surveillance cells that control the immune system and secrete influential bioactive molecules .
They sense changes in the local environment , and in response , they secrete large quantities of immunomodulatory agents to mitigate the body ’ s immune reaction as they secrete bioactive and extracellular matrix-building molecules to repair or regenerate damaged tissue .
In their @ @ @ @ @ @ @ from the nerve and secrete molecules that bind to opioid receptors .
Within minutes , the sense of pain dissipates.3,4 MSCs serve as powerful internal pharmaceutical factories that direct the body ’ s natural biological mechanisms to alleviate pain and activate tissue regeneration .
As scientists have more precisely defined the roles MSCs play in the body , Caplan has argued for a name change .
“ Instead of calling them ‘ mesenchymal stem cells , ’ I 've renamed them ‘ medicinal signaling cells , ’ '' said Caplan .
Caplan recognized @ @ @ @ @ @ @ a plethora of diseases and began to reach out to investors for help in funding MSC-based cell therapies .
Every day , scientists in academic laboratories make profound discoveries .
However , many of these discoveries never result in new medicines or treatments because many basic research scientists lack the network and capital needed to translate basic research into therapeutic products .
Additionally , many biopharmaceutical companies see early-stage basic research as a risky investment.5,6 In fact , in 2017 , venture-capitalist backed companies produced more approved drugs than traditional large-scale pharmaceutical companies.6 @ @ @ @ @ @ @ several investors .
Then he met Kevin Kimberlin , chairman of Spencer Trask & Co. , an advanced technology development firm with a legacy of helping engineers , scientists , and entrepreneurs develop scientific findings into market-leading companies .
Kimberlin was familiar with the potential for cellular therapy , having previously patented and developed the technical basis for the first approved cell-based immunotherapy with Jonas Salk of The Salk Institute of Biological Sciences .
“ We sensed that the MSCs might become a keystone in this new field of medicine , so we @ @ @ @ @ @ @ Caplan ’ s discovery , '' said Kimberlin .
In their first meeting , Caplan showed Kimberlin that he could isolate MSCs from bone marrow , expand their numbers in culture , and then infuse them to dock at specific sites of injury .
Within the body , the infused MSCs seemed to repair the bone and cartilage at the same time and in the appropriate locations .
“ I was impressed when he explained how our natural MSC population declines steadily as we get older , but that he could isolate and @ @ @ @ @ @ @ the regenerative ability of youth , ” said Kimberlin .
“ I said , ‘ You have discovered the ability to heal people ; I don ’ t know how we are going to build a company around this , but we have to try.
’ ” Together the two launched a biotech venture called Osiris Therapeutics Inc. , which they named after the Egyptian god of life and regeneration .
Osiris Therapeutics became the driving force behind several early MSC-based discoveries , expanding both scientific knowledge of these cells and development of @ @ @ @ @ @ @ cellular-matrix products emerged for treating skin ulcers , burns , severe wounds , and the first approved implantable cell-matrix product .
Most astonishingly , the Osiris researchers realized that the MSC could be fashioned into a drug delivery vehicle , serving as a drugstore for sites of injury .
In one influential early study , scientists at Osiris Therapeutics and their collaborators used MSCs to treat 12 children with steroid-resistant graft-versus-host disease ( GvHD ) .
Children with this disease suffer a violent immune reaction to hematopoietic stem-cell transplantation , where the body @ @ @ @ @ @ @ to peel away .
For the estimated 20 % of children who are resistant to pharmaceutical steroid treatment , GvHD disease is fatal .
In the Osiris trial , seven of the twelve children who received MSC transfusions showed complete remission from the disease at one month , and 95 % of the children lived at least six months , a dramatic improvement from the typical 25 % survival rate for children on traditional immunosuppressive treatments.8 In this study and in other early MCS cell therapy studies , researchers observed no adverse reactions,3 @ @ @ @ @ @ @ s first systemically delivered cell-therapy.7 Clinicians are now conducting trials to explore the utility of MSCs for treating COVID-19.9 One preliminary study conducted at Mount Sinai Hospital in New York City reported success with eleven out of thirteen critically ill COVID-19 patients .
The MSC treatment decreased inflammation , increased the number of virus-fighting T-cells , and repaired or regenerated lung tissue.10 “ Translating the MSC from an amazing insight into the first allogeneic cellular drug is a story that reminds us of why the work of basic scientists is so crucial and @ @ @ @ @ @ @ just as important , ” commented Kimberlin .
Today , there are approximately 1,195 clinical trials in progress exploring the use of MSCs to treat more than 900 conditions , including rheumatoid arthritis , acute myocardial infarct , stroke , Crohn 's disease , chronic heart failure , low back pain , and more .
“ The difference between traditional pharmaceuticals and cell-based therapy is that a pharmaceutical is a single drug , very highly purified , that has a very precise function .
Conversely , an MSC goes to sites of damage @ @ @ @ @ @ @ 's going on and then makes drugs , ” said Caplan .
“ We are at the beginning of what I hope will be hundreds of uses for MSCs to heal conditions which can not be treated any other way , ” said Kimberlin .
“ That is something we can all look forward to.
” “ There 's the joy of knowing that I had the right instinct to start a company because that 's the only way this technology would get the resources to move forward .
We are looking at @ @ @ @ @ @ @ can we make the horizon better and brighter ?
’ ” said Caplan .
Kimberlin commends Caplan for uncovering this new knowledge , sharing it , and encouraging others to add to and critique it .
His tireless work to translate these insights into products saved hundreds of children ’ s lives .
“ To me , this type of scientific innovation is the highest manifestation of moral good and Dr. Caplan exemplifies this noble purpose , ” concluded Kimberlin .
At the age of 78 , Caplan still ventures into his laboratory @ @ @ @ @ @ @ each week researching new ideas and discoveries .
“ I 'm an academic , and in a philosophical sense , my role in society is to continue to add new information .
And that 's how society progressed from the stone age to the current age .
We keep adding knowledge , and we keep turning the knowledge into wisdom .
I still do it because I can see the light at the end of the tunnel , ” said Caplan .
“ For a basic scientist to actually see his work provide @ @ @ @ @ @ @ 3 .
A. I. Caplan , “ Why are MSCs therapeutic ?
New data : new insight , ” Journal of Pathology , 217 : 318-324 , 2009 .
4 .
R. Somoza , D. Correa , and A.I .
Caplan , “ Roles for mesenchymal stem cells as medicinal signaling cells , ” Nature Protocols : Recipes for Researchers , 2016 .
Accessed October 11 , 2020. http : //www.nature.com/nprot/posters/msc/index.html 5 .
F. Sanchez-Guijo , et .
al.
, “ Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 @ @ @ @ @ @ @ of concept study , ” The Lancet , 25:100454 , 2020 .
6 .
W. Karpa and A. Grginovic , “ Long-term perspective on venture capital investments in early stage life-science projects related to health care , ” Economic Research-Ekonomska Istrazivanja , ( 33 ) 1:2526-2540 , 2020 .
8 .
K. Le Blanc , et .
al.
, “ Mesenchymal stem cells for treatment of steroid-resistant , severe , acute graft-versus-host disease : a phase II study , ” Lancet , 371:1579–1586 , 2008 .
9 .
K. Kimberlin , “ The @ @ @ @ @ @ @ The Wall Street Journal , 2020 .
Accessed October 11 , 2020. https : //www.wsj.com/articles/the-treatment-that-could-crush-covid-11597360709

The mysteries of a salamander regenerating its tail or a sea cucumber mending its organs have fascinated humans and perplexed scientists for centuries. The idea that the human body holds similar mechanisms to heal and repair itself is tantalizing and not altogether impossible. There are powerful cells called mesenchymal stem cells situated on the 50,000–100,000 miles of blood vessels in the human body. These cells carry the ability to initiate signaling cascades that drive tissue repair and regeneration.
In the mid-1960s, Marshall Urist, an orthopedic surgeon at the University of California Center for Health in Los Angeles, depleted all of the mineral calcium phosphate from pieces of bone. Urist took the remaining demineralized bone components and placed them into the muscle of an adult mouse and made the surprising discovery that bone could subsequently form in muscle tissue.1
In the late 1960s, Arnold Caplan, now professor of biology and director of the Skeletal Research Center at Case Western Reserve University, was perfecting a cell culture medium cocktail that converted cells he isolated from the presumptive wings and legs of chicken embryos into cartilage, bone, or muscle. His goal was to find the molecular signals that differentiated these cells into specialized tissue lineages.
When Caplan learned of Ursit’s results, he was intrigued. “I realized that there were stem cells—cells that could respond to powerful inductive molecules that must exist in the adult tissue,” said Caplan. “And so, coming from an orthopedic background, I knew that there were magic cells, magic elixirs, in bone marrow.”
Bone marrow has been associated with orthopedic healing since the days of Aristotle, and several studies in the mid-1960s suggested the existence of bone-related progenitor cells. Together with one of his post-doctoral researchers, Stephen Haynesworth, Caplan began purifying cells from human bone marrow in a search for cell types that make bone, relying on the same medium cocktail he perfected for embryonic chicken cells.2
“That magic medium was the whole trick to the entire mesenchymal stem cell technology,” said Caplan. “In that medium, the cells from bone marrow, which are very rare—one in 100,000, one in a million—stuck to the Petri dish and divided like wildfire.”
Medicinal Signaling Cells
Caplan and his team found that they could manipulate the adhered bone marrow cells to differentiate into muscle, cartilage, bone, or fat on tissue culture dishes. This ability to readily form a variety of cell types from the middle or mesenchymal layer of the body suggested a new type of adult stem cell, leading Caplan to coin the term “mesenchymal stem cell (MSC).” Colorized scanning electron micrograph (SEM) of a human mesenchymal stem cell (MSC)
“It turns out that that was a mistake,” said Caplan. Scientists at the time believed that cells behaved the same in tissue culture as they did within the body. “MSCs inside your body never differentiate the cartilage, never differentiate the bone, never differentiate the fat. So, in your body, these cells are not stem cells,” said Caplan. Instead, they are much more.
In the body, MSCs play an important role in maintaining stem or progenitor cell niches and homeostasis. They arise from perivascular cells called pericytes that reside on the surface of every blood vessel and act as a filter between blood vessels and tissues. If a blood vessel in any tissue becomes damaged, pericytes fall off the vessels and differentiate into MSCs that then orchestrate the formation of new vessels and tissues by recruiting and activating adult stem cells or progenitor cells that are already present in the tissue.3,4
“If you break a bone, there is a cell in your bone that is already there to make new bone. What the MSC does is pause that cell, give it a molecule to make it divide, and get it to make the new bone. The MSC doesn't make the new bone. The MSC is the instructor, the manager of the regeneration of every tissue,” said Caplan.
MSCs also act as surveillance cells that control the immune system and secrete influential bioactive molecules. They sense changes in the local environment, and in response, they secrete large quantities of immunomodulatory agents to mitigate the body’s immune reaction as they secrete bioactive and extracellular matrix-building molecules to repair or regenerate damaged tissue. In their surveillance, MSCs also detect pain signals from the nerve and secrete molecules that bind to opioid receptors. Within minutes, the sense of pain dissipates.3,4
MSCs serve as powerful internal pharmaceutical factories that direct the body’s natural biological mechanisms to alleviate pain and activate tissue regeneration. As scientists have more precisely defined the roles MSCs play in the body, Caplan has argued for a name change. “Instead of calling them ‘mesenchymal stem cells,’ I've renamed them ‘medicinal signaling cells,’" said Caplan.
Of Life and Resurrection
Caplan recognized the potential of these cells to treat a plethora of diseases and began to reach out to investors for help in funding MSC-based cell therapies. Every day, scientists in academic laboratories make profound discoveries. However, many of these discoveries never result in new medicines or treatments because many basic research scientists lack the network and capital needed to translate basic research into therapeutic products. Additionally, many biopharmaceutical companies see early-stage basic research as a risky investment.5,6 In fact, in 2017, venture-capitalist backed companies produced more approved drugs than traditional large-scale pharmaceutical companies.6
Initially, Caplan was turned down by several investors. Then he met Kevin Kimberlin, chairman of Spencer Trask & Co., an advanced technology development firm with a legacy of helping engineers, scientists, and entrepreneurs develop scientific findings into market-leading companies. Kimberlin was familiar with the potential for cellular therapy, having previously patented and developed the technical basis for the first approved cell-based immunotherapy with Jonas Salk of The Salk Institute of Biological Sciences. “We sensed that the MSCs might become a keystone in this new field of medicine, so we committed to find a way to commercialize Caplan’s discovery," said Kimberlin.
In their first meeting, Caplan showed Kimberlin that he could isolate MSCs from bone marrow, expand their numbers in culture, and then infuse them to dock at specific sites of injury. Within the body, the infused MSCs seemed to repair the bone and cartilage at the same time and in the appropriate locations.
“I was impressed when he explained how our natural MSC population declines steadily as we get older, but that he could isolate and multiply their number to possibly give us the regenerative ability of youth,” said Kimberlin. “I said, ‘You have discovered the ability to heal people; I don’t know how we are going to build a company around this, but we have to try.’” Together the two launched a biotech venture called Osiris Therapeutics Inc., which they named after the Egyptian god of life and regeneration.
Osiris Therapeutics became the driving force behind several early MSC-based discoveries, expanding both scientific knowledge of these cells and development of real-world therapies. A broad portfolio of cellular-matrix products emerged for treating skin ulcers, burns, severe wounds, and the first approved implantable cell-matrix product. Most astonishingly, the Osiris researchers realized that the MSC could be fashioned into a drug delivery vehicle, serving as a drugstore for sites of injury.
Scientist working in a lab
In one influential early study, scientists at Osiris Therapeutics and their collaborators used MSCs to treat 12 children with steroid-resistant graft-versus-host disease (GvHD). Children with this disease suffer a violent immune reaction to hematopoietic stem-cell transplantation, where the body attacks itself, causing the intestinal lining to peel away. For the estimated 20% of children who are resistant to pharmaceutical steroid treatment, GvHD disease is fatal. In the Osiris trial, seven of the twelve children who received MSC transfusions showed complete remission from the disease at one month, and 95% of the children lived at least six months, a dramatic improvement from the typical 25% survival rate for children on traditional immunosuppressive treatments.8 In this study and in other early MCS cell therapy studies, researchers observed no adverse reactions,3 and this approach became the world’s first systemically delivered cell-therapy.7
Clinicians are now conducting trials to explore the utility of MSCs for treating COVID-19.9 One preliminary study conducted at Mount Sinai Hospital in New York City reported success with eleven out of thirteen critically ill COVID-19 patients. The MSC treatment decreased inflammation, increased the number of virus-fighting T-cells, and repaired or regenerated lung tissue.10
“Translating the MSC from an amazing insight into the first allogeneic cellular drug is a story that reminds us of why the work of basic scientists is so crucial and why developing fundamental science into practice is just as important,” commented Kimberlin.
Today, there are approximately 1,195 clinical trials in progress exploring the use of MSCs to treat more than 900 conditions, including rheumatoid arthritis, acute myocardial infarct, stroke, Crohn's disease, chronic heart failure, low back pain, and more. “The difference between traditional pharmaceuticals and cell-based therapy is that a pharmaceutical is a single drug, very highly purified, that has a very precise function. Conversely, an MSC goes to sites of damage, looks around, analyzes everything that's going on and then makes drugs,” said Caplan.
“We are at the beginning of what I hope will be hundreds of uses for MSCs to heal conditions which cannot be treated any other way,” said Kimberlin. “That is something we can all look forward to.”
“There's the joy of knowing that I had the right instinct to start a company because that's the only way this technology would get the resources to move forward. We are looking at the horizon and saying, ‘How can we make the horizon better and brighter?’” said Caplan.
Kimberlin commends Caplan for uncovering this new knowledge, sharing it, and encouraging others to add to and critique it. His tireless work to translate these insights into products saved hundreds of children’s lives.
“To me, this type of scientific innovation is the highest manifestation of moral good and Dr. Caplan exemplifies this noble purpose,” concluded Kimberlin.
At the age of 78, Caplan still ventures into his laboratory every day, often spending 60-80 hours each week researching new ideas and discoveries. “I'm an academic, and in a philosophical sense, my role in society is to continue to add new information. And that's how society progressed from the stone age to the current age. We keep adding knowledge, and we keep turning the knowledge into wisdom. I still do it because I can see the light at the end of the tunnel,” said Caplan. “For a basic scientist to actually see his work provide medical therapy is an enormous gift.”
References
1. M.R. Urist, “Bone: Formation by autoinduction,” Science, 150:893–899, 1965.
2. A. I. Caplan, “Mesenchymal Stem Cells: Time to Change the Name!” Stem Cell Translational Medicine, 6:1445-1451, 2017.
3. A. I. Caplan, “Why are MSCs therapeutic? New data: new insight,” Journal of Pathology, 217: 318-324, 2009.
4. R. Somoza, D. Correa, and A.I. Caplan, “Roles for mesenchymal stem cells as medicinal signaling cells,” Nature Protocols: Recipes for Researchers, 2016. Accessed October 11, 2020. http://www.nature.com/nprot/posters/msc/index.html
5. F. Sanchez-Guijo, et. al., “Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study,” The Lancet, 25:100454, 2020.
6. W. Karpa and A. Grginovic, “Long-term perspective on venture capital investments in early stage life-science projects related to health care,” Economic Research-Ekonomska Istrazivanja, (33)1:2526-2540, 2020.
7. Osiris Therapeutics Inc., “Timeline Express Announcements Archive,” Accessed October 11, 2020. http://www.osiris.com/announcement/
8. K. Le Blanc, et. al., “Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study,” Lancet, 371:1579–1586, 2008.
9. K. Kimberlin, “The Treatment That Could Crush COVID,” The Wall Street Journal, 2020. Accessed October 11, 2020. https://www.wsj.com/articles/the-treatment-that-could-crush-covid-11597360709
10. R. Murphey, “Biopharma VC Basics 1: What do VCs do?” Bay Bridge Bio, 2020. Accessed October 11, 2020. https://www.baybridgebio.com/blog/vc_basics_1.html


thescientist--2020-11-17--Breastmilk Harbors Antibodies to SARS-CoV-2

Milk from lactating moms may hold potent antibodies to counter SARS-CoV-2 infections , according to a new study of 15 women .
All of the samples from women who had recovered from COVID-19 and who were breastfeeding babies at the time had antibodies reactive to the virus ’ s spike protein , researchers report in the November issue of iScience .
Detecting antibodies against the virus in breastmilk indicates that mothers could be passing viral immunity to their babies .
Women can “ feel pretty comfortable breastfeeding ” during the pandemic , Christina Chambers , a perinatal epidemiologist at the @ @ @ @ @ @ @ who not involved in the new study , tells The Scientist .
To date , there ’ s no evidence that a mother can transmit SARS-CoV-2 to her baby through breastmilk , Chambers says .
She and others have tested breastmilk for SARS-CoV-2 RNA and found a few positive results , but no live virus .
Her latest research also suggests that donor milk is safe for babies ’ consumption , too , though she hasn ’ t assessed antibodies in donor milk banks she works with yet .
Antibodies in breastmilk may @ @ @ @ @ @ @ infants from the virus .
Antibodies extracted from milk—as opposed to the current practice of using convalescent serum—could also serve as a therapeutic for COVID-19 .
However , “ people question that this is something that could really happen , ” says study coauthor Rebecca Powell , an immunologist at the Icahn School of Medicine at Mount Sinai in New York City .
Because there isn ’ t a wider understanding of the immune benefits of breastmilk , she says , the concept has not caught on in antiviral drug development .
Powell @ @ @ @ @ @ @ the past four years and was analyzing how the seasonal flu vaccine prompted an immune response in breastmilk when the coronavirus pandemic spread to New York City earlier this year .
Switching to study the SARS-CoV-2 immune response in breastmilk was “ a no brainer , ” she says .
“ There ’ s so many unanswered questions in general about milk immunology , but to be able to study it with a novel pathogen was really important.
” By early April , she and her colleagues had received approval to begin collecting @ @ @ @ @ @ @ recovered from COVID-19 .
The researchers collected samples from eight women who had a SARS-CoV-2–positive PCR test and seven who had suspected cases of the disease but were not tested ; all 15 were lactating at the time .
The team then compared the samples to ones from different lactating mothers amassed before the pandemic began , first assessing them for the presence of immunoglobulin A ( IgA ) antibodies using an enzyme-linked immunosorbent assay ( ELISA ) and then checking the ability of any antibodies found to bind to the SARS-CoV-2 spike @ @ @ @ @ @ @ the women who had recovered from COVID-19 had specific SARS-CoV-2 binding activity , while the pre-pandemic samples had low levels of nonspecific or cross-reactive activity , the researchers report .
They next tested the antibodies ’ response to the receptor binding domain of the SARS-CoV-2 spike protein , and found that 12 out of 15 of the samples from previously-infected donors showed significant IgA binding activity .
Some of those samples also included other reactive antibodies such as immunoglobulin G and immunoglobulin M. Compared with the controls , it was IgA and IgG @ @ @ @ @ @ @ results align with a study published in September in the Journal of Perinatology that also detected high levels of IgA and some IgG and IgM that were reactive to the S1 and S2 subunits of the SARS-CoV-2 spike protein in a majority of milk samples collected during the pandemic .
None of the breastmilk tested positive for SARS-CoV-2 with a PCR test , suggesting none of the mothers were infected at the time of sample collection .
There was also no documentation of whether the 41 women who donated samples had ever been @ @ @ @ @ @ @ coauthor Veronique Demers-Mathieu , an immunologist at Medolac Laboratories in Boulder City , Nevada , so it ’ s unclear if these antibodies were the result of SARS-CoV-2 or another viral infection .
The team did collect general health information on the donors of the milk samples and found that S1 and S2 SARS-CoV-2–reactive IgG levels were higher in milk from women who had had symptoms of a viral respiratory infection during the last year than in milk from women who hadn ’ t had any symptoms of infection .
IgG abundance was @ @ @ @ @ @ @ than from those taken in 2018 , long before the pandemic started .
The IgA and IgM antibody reactivity , however , didn ’ t appear to be specific to SARS-CoV-2 S1 and S2 and did not differ between the 2020 samples and the 2018 samples , meaning these responses could be the result of cross-reactivity from antibodies generated after exposure to other viruses .
That suggests the antibodies secreted in breastmilk provide a broad immunity to breastfeeding infants , Demers-Mathieu says .
One important feature of these antibodies , whether specific to @ @ @ @ @ @ @ they are secretory antibodies , Powell notes .
The B cells that secrete antibodies into milk originate from the mucosal immune system in the mother ’ s small intestine .
Those B cells travel through the blood to the mammary glands and secrete IgA that ’ s then shuttled from the mammary tissue to the milk via a transporter protein .
Those proteins , called secretory components , leave pieces of themselves on the antibodies , wrapping around them and protecting them from being degraded in the infant mouth and gut .
“ @ @ @ @ @ @ @ milk , but in saliva and all other mucosal secretions , ” Powell explains .
“ It ’ s not unique to milk , but it is not what you find in the blood.
” That difference could give breastmilk-derived antibodies an advantage over blood-based ones as far as therapeutic options go , she explains .
Antibodies such as IgG that are extracted from serum and transfused into the blood of a sick person travel throughout the body and might not go where they are needed .
But secretory antibodies , such as @ @ @ @ @ @ @ and then inhaled into the respiratory tract—just where those antibodies are needed in COVID-19 .
Because of the protective secretory component they have , these antibodies can endure in the mucosa and target the virus , Powell explains .
“ What we are finding in the milk is unique compared to what many people have already studied in the blood in terms of antibody response , ” she says .
Research suggests that blood-derived antibodies can last months .
Secretory antibodies in breastmilk might last longer , Powell ’ s most recent data @ @ @ @ @ @ @ be a longer window to collect antibodies from lactating donors after they ’ ve recovered from COVID-19 .
Neither Demers-Mathieu ’ s nor Powell ’ s studies tested whether the breastmilk antibodies could neutralize SARS-CoV-2 , which is a next step in both teams ’ research .
Powell has early results suggesting the breastmilk antibodies do neutralize the virus , and a company called Lactiga has partnered with her to continue developing the idea of extracting antibodies from breastmilk to counter COVID-19 .
“ I think the potential is really great , ” @ @ @ @ @ @ @ past this taboo that it ’ s breastmilk .
”

ABOVE: © ISTOCK.COM, FLY VIEW PRODUCTIONS
Milk from lactating moms may hold potent antibodies to counter SARS-CoV-2 infections, according to a new study of 15 women. All of the samples from women who had recovered from COVID-19 and who were breastfeeding babies at the time had antibodies reactive to the virus’s spike protein, researchers report in the November issue of iScience.
Detecting antibodies against the virus in breastmilk indicates that mothers could be passing viral immunity to their babies. Women can “feel pretty comfortable breastfeeding” during the pandemic, Christina Chambers, a perinatal epidemiologist at the University of California, San Diego, who not involved in the new study, tells The Scientist.
To date, there’s no evidence that a mother can transmit SARS-CoV-2 to her baby through breastmilk, Chambers says. She and others have tested breastmilk for SARS-CoV-2 RNA and found a few positive results, but no live virus. Her latest research also suggests that donor milk is safe for babies’ consumption, too, though she hasn’t assessed antibodies in donor milk banks she works with yet.
I think the potential is really great, if we get past this taboo that it’s breastmilk. —Rebecca Powell, Icahn School of Medicine at Mount Sina i
Antibodies in breastmilk may be useful for more than protecting nursing infants from the virus. Antibodies extracted from milk—as opposed to the current practice of using convalescent serum—could also serve as a therapeutic for COVID-19. However, “people question that this is something that could really happen,” says study coauthor Rebecca Powell, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City. Because there isn’t a wider understanding of the immune benefits of breastmilk, she says, the concept has not caught on in antiviral drug development.
Detecting breastmilk antibodies
Powell has been investigating human milk immunology for the past four years and was analyzing how the seasonal flu vaccine prompted an immune response in breastmilk when the coronavirus pandemic spread to New York City earlier this year. Switching to study the SARS-CoV-2 immune response in breastmilk was “a no brainer,” she says. “There’s so many unanswered questions in general about milk immunology, but to be able to study it with a novel pathogen was really important.”
By early April, she and her colleagues had received approval to begin collecting milk samples from lactating mothers who had recovered from COVID-19. The researchers collected samples from eight women who had a SARS-CoV-2–positive PCR test and seven who had suspected cases of the disease but were not tested; all 15 were lactating at the time. The team then compared the samples to ones from different lactating mothers amassed before the pandemic began, first assessing them for the presence of immunoglobulin A (IgA) antibodies using an enzyme-linked immunosorbent assay (ELISA) and then checking the ability of any antibodies found to bind to the SARS-CoV-2 spike protein.
All the of samples from the women who had recovered from COVID-19 had specific SARS-CoV-2 binding activity, while the pre-pandemic samples had low levels of nonspecific or cross-reactive activity, the researchers report. They next tested the antibodies’ response to the receptor binding domain of the SARS-CoV-2 spike protein, and found that 12 out of 15 of the samples from previously-infected donors showed significant IgA binding activity. Some of those samples also included other reactive antibodies such as immunoglobulin G and immunoglobulin M. Compared with the controls, it was IgA and IgG levels that were the highest.
The results align with a study published in September in the Journal of Perinatology that also detected high levels of IgA and some IgG and IgM that were reactive to the S1 and S2 subunits of the SARS-CoV-2 spike protein in a majority of milk samples collected during the pandemic. None of the breastmilk tested positive for SARS-CoV-2 with a PCR test, suggesting none of the mothers were infected at the time of sample collection.
There was also no documentation of whether the 41 women who donated samples had ever been infected with the virus, notes study coauthor Veronique Demers-Mathieu, an immunologist at Medolac Laboratories in Boulder City, Nevada, so it’s unclear if these antibodies were the result of SARS-CoV-2 or another viral infection.
The team did collect general health information on the donors of the milk samples and found that S1 and S2 SARS-CoV-2–reactive IgG levels were higher in milk from women who had had symptoms of a viral respiratory infection during the last year than in milk from women who hadn’t had any symptoms of infection. IgG abundance was also higher in the samples from 2020 than from those taken in 2018, long before the pandemic started. The IgA and IgM antibody reactivity, however, didn’t appear to be specific to SARS-CoV-2 S1 and S2 and did not differ between the 2020 samples and the 2018 samples, meaning these responses could be the result of cross-reactivity from antibodies generated after exposure to other viruses. That suggests the antibodies secreted in breastmilk provide a broad immunity to breastfeeding infants, Demers-Mathieu says.
Benefits of breastmilk versus blood antibodies
One important feature of these antibodies, whether specific to the virus or not, is that they are secretory antibodies, Powell notes. The B cells that secrete antibodies into milk originate from the mucosal immune system in the mother’s small intestine. Those B cells travel through the blood to the mammary glands and secrete IgA that’s then shuttled from the mammary tissue to the milk via a transporter protein. Those proteins, called secretory components, leave pieces of themselves on the antibodies, wrapping around them and protecting them from being degraded in the infant mouth and gut. “Secretory antibody is found not only in milk, but in saliva and all other mucosal secretions,” Powell explains. “It’s not unique to milk, but it is not what you find in the blood.”
That difference could give breastmilk-derived antibodies an advantage over blood-based ones as far as therapeutic options go, she explains. Antibodies such as IgG that are extracted from serum and transfused into the blood of a sick person travel throughout the body and might not go where they are needed. But secretory antibodies, such as IgA from breastmilk, could be extracted and then inhaled into the respiratory tract—just where those antibodies are needed in COVID-19. Because of the protective secretory component they have, these antibodies can endure in the mucosa and target the virus, Powell explains.
“What we are finding in the milk is unique compared to what many people have already studied in the blood in terms of antibody response,” she says. Research suggests that blood-derived antibodies can last months. Secretory antibodies in breastmilk might last longer, Powell’s most recent data indicate, and that means there could be a longer window to collect antibodies from lactating donors after they’ve recovered from COVID-19.
Neither Demers-Mathieu’s nor Powell’s studies tested whether the breastmilk antibodies could neutralize SARS-CoV-2, which is a next step in both teams’ research. Powell has early results suggesting the breastmilk antibodies do neutralize the virus, and a company called Lactiga has partnered with her to continue developing the idea of extracting antibodies from breastmilk to counter COVID-19.
“I think the potential is really great,” says Powell, “if we get past this taboo that it’s breastmilk.”


thescientist--2020-11-18--Q&A: Study Quantifies LGBQ Representation in STEM Degrees, Jobs

Research has long shown the existence of persistent gender and racial gaps—women and non-whites tend to be underrepresented—for achievements in STEM .
While anecdotal evidence and some studies have shown a similar pattern with regard to the LGBQ community , few studies have directly compared STEM outcomes by people in the LGBQ community to those of heterosexual individuals because of a lack of detailed data about sexual orientation .
A report published today ( November 18 ) in PLOS ONE studied US census data of 142,641 individuals in same-sex couples to quantify their representation in STEM and found a large @ @ @ @ @ @ @ same-sex couples and men in heterosexual couples who have STEM degrees or occupations .
The data show that men in same-sex couples are 12 percentage points less likely to have completed a bachelor ’ s degree in a STEM field compared to men partnered with women .
The researchers observed no difference between women in same-sex couples and women in heterosexual couples in terms of STEM degree completion ; however , they found that women in same-sex couples are two percentage points more likely to work in a STEM field than women in @ @ @ @ @ @ @ Christopher Carpenter , a health economist at Vanderbilt University and a coauthor of the new study , about the findings .
The Scientist : What inspired you to want to dive into sexual minority representation in STEM fields ?
Christopher Carpenter : I have a really deep passion for understanding demographic and socioeconomic differences for sexual minority populations relative to heterosexual populations .
I ’ ve studied wage differences for gay and bisexual men for the last 20 years or so .
My coauthor on the study , Dario Sansone , who is @ @ @ @ @ @ @ Exeter , also shares these interests in understanding LGBT populations and worked here at Vanderbilt with me last year as a postdoc .
He has a separate interest in STEM education and advancement of different marginalized groups in STEM , so combining that interest with our joint interest in LGBT populations is the underlying motivation for this study .
TS : How does this study tie into some of the other work that you or your coauthor have done ?
CC : Dr. Sansone has a separate paper looking at the experiences of @ @ @ @ @ @ @ heterosexual college students .
I have a much older paper also looking at economic college outcomes for sexual minority students , but most of my work has really looked at earnings and occupation effects .
In many ways , looking at STEM specifically is just a very interesting example of good labor market outcomes that people have and whether those are different by sexual orientation .
In many senses , you can think of STEM outcomes in the labor market as particularly good outcomes because they require lots of education , they are @ @ @ @ @ @ @ .
So the fact that we find that the men in same-sex couples in particular are significantly less likely to have those outcomes tells us something about relative social position of sexual minorities .
TS : What was the gap in the literature you were hoping to address with this study ?
CC : There was major gap—a data limitation gap .
People have been interested in this question for a long time , but understanding where to find large samples of sexual minorities in credible social sciences datasets that have good measures @ @ @ @ @ @ @ has been a real challenge .
To be perfectly blunt , sexual minorities are a small share of the total population , so you need gigantic sample sizes in order to really credibly say something meaningful about subgroups .
Prior research has been based on much smaller samples—it ’ s good research—but it ’ s sometimes been qualitative-focused , sometimes just focusing on a couple hundred or fewer people , but you know our ability to look at outcomes that are objectively measured for tens of thousands of people in the same-sex couples @ @ @ @ @ @ @ .
TS : Tell me more about the American Community Survey , from which you pull data for your study .
CC : As I said before , the main challenge in studying LGBT populations in general is finding datasets that have big enough samples of sexual minorities .
The American Community Survey solves that problem in many dimensions .
It is a product of the United States Census Bureau , so every 10 years or so everyone ’ s getting their form in their mailbox and enumerating who ’ s in their @ @ @ @ @ @ @ how much money they make , and for a couple of decades now the Census Bureau has included additional information and that allows researchers to know the relationship of individuals within the household .
[ Editor ’ s note : While the census is administered every 10 years , the American Community Survey is administered annually . ]
So what you can do with these data for the first time in social science research is identify households where the main householder is of the same sex of another person and when the other @ @ @ @ @ @ @ to that householder , it is described as “ spouse ” or “ unmarried partner.
” Using the information on the sex composition and the relationships to each other in the household , you can identify couples who , through other datasets , we have confirmed with very high degree of certainty are sexual minorities in same-sex couples .
Now to be clear , you only get coupled sexual minorities and so that is a limitation of the study .
I can ’ t tell you something about people who are not in @ @ @ @ @ @ @ that because it basically is a survey that goes to hundreds of thousands of people every single year , you can find the needle in the haystack .
TS : Why do you think there ’ s a bigger discrepancy between men in same-sex couples and men in heterosexual couples pursuing a STEM-related degree and occupation , as compared to women ?
CC : We don ’ t know the full answer .
Another point to make clear is : we do not find a significant difference for women in same-sex couples compared @ @ @ @ @ @ @ , all women , regardless of their couple status , are much less likely to have STEM degrees and occupations .
I want to be very clear that the gender gap in STEM outcomes , which is experienced both by lesbian women and by heterosexual women , are way bigger than the magnitude of the sexual orientation difference that we find for men in same-sex couples .
.
.
.
As to what ’ s going on there , there ’ s a lot of evidence actually in economics literature that lesbians do @ @ @ @ @ @ @ to heterosexual women with similar skills then gay men compared to heterosexual men with similar skills .
For example , lots of economic research shows that gay men suffer a penalty in wages , but lesbians experience a premium in wages relative to a similarly situated , same-gender counterparts , who are heterosexual .
And why does that occur ?
… So suppose if you thought , for example , that lesbians are traditionally more masculine and gay men are traditionally less masculine—if masculinity is rewarded in the labor market and rewarded in @ @ @ @ @ @ @ explanation for why you see these relative differences—this penalty experience for gay men that is not observed for lesbians .
But I have to say that ’ s a pretty crude explanation that is not always borne out in fact .
We ’ re not saying that all gay men are feminine , we ’ re not saying that all lesbians are masculine , but to the extent that people have those perceptions , that could be one contributing factor .
TS : How are these findings tied to the large gender gap @ @ @ @ @ @ @ ’ s a great question .
I want to highlight what I think is one of the most intriguing findings of our paper : we find very clear evidence that the [ proportion of ] men in same sex-couples [ in STEM ] relative to men in different-sex couples , which for convenience I ’ m going to call the ‘ gay male STEM gap , ’ is systematically positively related to the relative representation of women in those same fields .
So the more representation of women in those fields , the @ @ @ @ @ @ @ ] gap— [ that is , ] the more representation of men in same-sex couples relative to men in different-sex couples .
That tells us is that there is something fundamental underlying these two gaps that is related .
It is a road too far for us to conclude that the things that would alleviate the gender gap would also alleviate the gay male STEM gap , but our results are at least consistent with the possibility that that may be true .
So , what do we know reduces the gender gap @ @ @ @ @ @ @ interventions—this is a bit outside my direct research area—but we know that some types of interventions that reduce toxic masculinity within STEM departments , for example , might be good improving outcomes for women and , potentially , given our results for gay men , things like sexual harassment reduction ; equity , diversity , and inclusion training—to the extent that those things do help solve the gender gap in STEM , those are some of the same interventions that could be potentially helpful at addressing this new gap we ’ ve discovered @ @ @ @ @ @ @ will read your paper and take your findings to heart ?
CC : One is people who think a lot about graduate and undergraduate education in STEM fields , and that ’ s a lot of education researchers and a lot of government folks .
Adding sexual orientation into the mix is a very important result of our study , and we want all of those folks to be aware that we need to be thinking not only about sexual orientation independently , but also intersectionality between sexual orientation and race and gender @ @ @ @ @ @ @ gender identity or transgender status despite that a natural implication of our study is that almost surely there ’ s the same problem for transgender-identified folks as well .
See : “ Black in X Addresses Long-Standing Inequity in STEM ” So why do I think that higher education administrators and government folks working in education should be the audience of our study ?
Well , one very concrete reason is because the way we know what we know about the pipeline in STEM is from surveys of college students and people who @ @ @ @ @ @ @ Those surveys don ’ t include any information on sexual orientation currently , so there are discussions to add sexual orientation and gender identity to these major surveys of the federal government like the Survey of Earned Doctorates and the National Survey of College Graduates .
D. Sansone , C.S .
Carpenter , “ Turing ’ s children : Representation of sexual minorities in STEM , ” PLOS ONE , doi:10.1371/journal.pone.0241596 , 2020 .
Editor ’ s note : The interview was edited for brevity .

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MEDITERRANEAN
Research has long shown the existence of persistent gender and racial gaps—women and non-whites tend to be underrepresented—for achievements in STEM. While anecdotal evidence and some studies have shown a similar pattern with regard to the LGBQ community, few studies have directly compared STEM outcomes by people in the LGBQ community to those of heterosexual individuals because of a lack of detailed data about sexual orientation.
A report published today (November 18) in PLOS ONE studied US census data of 142,641 individuals in same-sex couples to quantify their representation in STEM and found a large difference between the proportion of men in same-sex couples and men in heterosexual couples who have STEM degrees or occupations. The data show that men in same-sex couples are 12 percentage points less likely to have completed a bachelor’s degree in a STEM field compared to men partnered with women.
The researchers observed no difference between women in same-sex couples and women in heterosexual couples in terms of STEM degree completion; however, they found that women in same-sex couples are two percentage points more likely to work in a STEM field than women in heterosexual couples.
The Scientist spoke with Christopher Carpenter, a health economist at Vanderbilt University and a coauthor of the new study, about the findings.
The Scientist: What inspired you to want to dive into sexual minority representation in STEM fields?
Christopher Carpenter VANDERBILT UNIVERSITY
Christopher Carpenter: I have a really deep passion for understanding demographic and socioeconomic differences for sexual minority populations relative to heterosexual populations. I’ve studied wage differences for gay and bisexual men for the last 20 years or so. My coauthor on the study, Dario Sansone, who is now a lecturer at the University of Exeter, also shares these interests in understanding LGBT populations and worked here at Vanderbilt with me last year as a postdoc. He has a separate interest in STEM education and advancement of different marginalized groups in STEM, so combining that interest with our joint interest in LGBT populations is the underlying motivation for this study.
TS: How does this study tie into some of the other work that you or your coauthor have done?
CC: Dr. Sansone has a separate paper looking at the experiences of how LGBT college students fare relative to heterosexual college students. I have a much older paper also looking at economic college outcomes for sexual minority students, but most of my work has really looked at earnings and occupation effects. In many ways, looking at STEM specifically is just a very interesting example of good labor market outcomes that people have and whether those are different by sexual orientation. In many senses, you can think of STEM outcomes in the labor market as particularly good outcomes because they require lots of education, they are generally highly compensated, generally high prestige. So the fact that we find that the men in same-sex couples in particular are significantly less likely to have those outcomes tells us something about relative social position of sexual minorities.
TS: What was the gap in the literature you were hoping to address with this study?
CC: There was major gap—a data limitation gap. People have been interested in this question for a long time, but understanding where to find large samples of sexual minorities in credible social sciences datasets that have good measures of sexual orientation and STEM degree status has been a real challenge. To be perfectly blunt, sexual minorities are a small share of the total population, so you need gigantic sample sizes in order to really credibly say something meaningful about subgroups.
Prior research has been based on much smaller samples—it’s good research—but it’s sometimes been qualitative-focused, sometimes just focusing on a couple hundred or fewer people, but you know our ability to look at outcomes that are objectively measured for tens of thousands of people in the same-sex couples is the real advance of our study.
TS: Tell me more about the American Community Survey, from which you pull data for your study.
CC: As I said before, the main challenge in studying LGBT populations in general is finding datasets that have big enough samples of sexual minorities. The American Community Survey solves that problem in many dimensions. It is a product of the United States Census Bureau, so every 10 years or so everyone’s getting their form in their mailbox and enumerating who’s in their household, how old they are, how much money they make, and for a couple of decades now the Census Bureau has included additional information and that allows researchers to know the relationship of individuals within the household. [Editor’s note: While the census is administered every 10 years, the American Community Survey is administered annually.]
So what you can do with these data for the first time in social science research is identify households where the main householder is of the same sex of another person and when the other person’s relationship is described relative to that householder, it is described as “spouse” or “unmarried partner.” Using the information on the sex composition and the relationships to each other in the household, you can identify couples who, through other datasets, we have confirmed with very high degree of certainty are sexual minorities in same-sex couples.
Now to be clear, you only get coupled sexual minorities and so that is a limitation of the study. I can’t tell you something about people who are not in same-sex relationships, but the advantage is that because it basically is a survey that goes to hundreds of thousands of people every single year, you can find the needle in the haystack.
TS: Why do you think there’s a bigger discrepancy between men in same-sex couples and men in heterosexual couples pursuing a STEM-related degree and occupation, as compared to women?
I want to be very clear that the gender gap in STEM outcomes, which is experienced both by lesbian women and by heterosexual women, are way bigger than the magnitude of the sexual orientation difference that we find for men in same-sex couples.
CC: We don’t know the full answer. Another point to make clear is: we do not find a significant difference for women in same-sex couples compared to women in different-sex couples. However, all women, regardless of their couple status, are much less likely to have STEM degrees and occupations. I want to be very clear that the gender gap in STEM outcomes, which is experienced both by lesbian women and by heterosexual women, are way bigger than the magnitude of the sexual orientation difference that we find for men in same-sex couples. . . .
As to what’s going on there, there’s a lot of evidence actually in economics literature that lesbians do better in the labor market when compared to heterosexual women with similar skills then gay men compared to heterosexual men with similar skills. For example, lots of economic research shows that gay men suffer a penalty in wages, but lesbians experience a premium in wages relative to a similarly situated, same-gender counterparts, who are heterosexual. And why does that occur? … So suppose if you thought, for example, that lesbians are traditionally more masculine and gay men are traditionally less masculine—if masculinity is rewarded in the labor market and rewarded in STEM departments, that might be an explanation for why you see these relative differences—this penalty experience for gay men that is not observed for lesbians.
But I have to say that’s a pretty crude explanation that is not always borne out in fact. We’re not saying that all gay men are feminine, we’re not saying that all lesbians are masculine, but to the extent that people have those perceptions, that could be one contributing factor.
TS: How are these findings tied to the large gender gap in STEM fields?
CC: That’s a great question. I want to highlight what I think is one of the most intriguing findings of our paper: we find very clear evidence that the [proportion of] men in same sex-couples [in STEM] relative to men in different-sex couples, which for convenience I’m going to call the ‘gay male STEM gap,’ is systematically positively related to the relative representation of women in those same fields. So the more representation of women in those fields, the smaller is the [gay male STEM] gap—[that is,] the more representation of men in same-sex couples relative to men in different-sex couples.
That tells us is that there is something fundamental underlying these two gaps that is related. It is a road too far for us to conclude that the things that would alleviate the gender gap would also alleviate the gay male STEM gap, but our results are at least consistent with the possibility that that may be true.
So, what do we know reduces the gender gap? We know that some types of interventions—this is a bit outside my direct research area—but we know that some types of interventions that reduce toxic masculinity within STEM departments, for example, might be good improving outcomes for women and, potentially, given our results for gay men, things like sexual harassment reduction; equity, diversity, and inclusion training—to the extent that those things do help solve the gender gap in STEM, those are some of the same interventions that could be potentially helpful at addressing this new gap we’ve discovered.
TS: Who do you hope will read your paper and take your findings to heart?
CC: One is people who think a lot about graduate and undergraduate education in STEM fields, and that’s a lot of education researchers and a lot of government folks. Adding sexual orientation into the mix is a very important result of our study, and we want all of those folks to be aware that we need to be thinking not only about sexual orientation independently, but also intersectionality between sexual orientation and race and gender. Our study unfortunately says nothing about gender identity or transgender status despite that a natural implication of our study is that almost surely there’s the same problem for transgender-identified folks as well.
So why do I think that higher education administrators and government folks working in education should be the audience of our study? Well, one very concrete reason is because the way we know what we know about the pipeline in STEM is from surveys of college students and people who are successful in getting graduate degrees. Those surveys don’t include any information on sexual orientation currently, so there are discussions to add sexual orientation and gender identity to these major surveys of the federal government like the Survey of Earned Doctorates and the National Survey of College Graduates.
D. Sansone, C.S. Carpenter, “Turing’s children: Representation of sexual minorities in STEM,” PLOS ONE, doi:10.1371/journal.pone.0241596, 2020.
Editor’s note: The interview was edited for brevity.


thescientist--2020-11-18--Gray Wolf Reintroduction in Colorado Encounters Federal Kerfuffle

Mere days before voters in Colorado this month approved the reintroduction of gray wolves into the wild , the US Department of the Interior announced that wolf numbers had recovered and would no longer receive federal protection under the Endangered Species Act as of January 4 , 2021 .
Although lawsuits will be filed in the next month or so to reverse DOI ’ s decision , delisting would have both positive and negative consequences on reintroduction efforts .
According to the wording of the state ’ s Proposition 114 , Colorado Parks and Wildlife Commission would be responsible for @ @ @ @ @ @ @ and would need to begin carrying it out before December 31 , 2023 , along with compensating farmers for lost livestock .
According to NPR , this was the first time any state had planned to take individual action on an endangered species .
This in itself sparked debate about who should be in charge of reintroduction plans : voters or conservation officials .
The measure did pass on November 3 by a slight margin , but the DOI ’ s announcement on October 26 has complicated the endeavor to boost wolf numbers @ @ @ @ @ @ @ ’ s statement justified delisting the wolves by saying that with more than 6,000 gray wolves now living in the contiguous United States , recovery efforts have “ greatly exceeded ” the goals that had been set forth by the agency .
One aspect that will make Prop .
114 ’ s implementation easier is the fact that if the animal is not a protected species , there are fewer hoops to jump through with getting the permits to send them into the wild .
“ So it ’ s an ironic benefit @ @ @ @ @ @ @ with delisting wolves in the first place , ” Rob Edward , president of the Rocky Mountain Wolf Action Fund , tells The Daily Sentinel .
While the paperwork might become easier without having to go through federal channels , a significant amount of money to help make the transition a success would no longer be available if the wolves aren ’ t on the endangered species list anymore .
Edward tells the Sentinel that as much as 75 percent of the funding for the project was expected to come from the federal @ @ @ @ @ @ @ some federal money available , it isn ’ t as clear where the bulk of the funding will come from or how the program will proceed .
The Denver Gazette reports that Michael Robinson , a senior conservation advocate with the Center for Biological Diversity , says he does not believe that President-Elect Joe Biden ’ s incoming administration is likely to reverse the decision made by the current administration .

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Mere days before voters in Colorado this month approved the reintroduction of gray wolves into the wild, the US Department of the Interior announced that wolf numbers had recovered and would no longer receive federal protection under the Endangered Species Act as of January 4, 2021. Although lawsuits will be filed in the next month or so to reverse DOI’s decision, delisting would have both positive and negative consequences on reintroduction efforts.
According to the wording of the state’s Proposition 114, Colorado Parks and Wildlife Commission would be responsible for devising a reintroduction plan for the wolves and would need to begin carrying it out before December 31, 2023, along with compensating farmers for lost livestock. According to NPR, this was the first time any state had planned to take individual action on an endangered species. This in itself sparked debate about who should be in charge of reintroduction plans: voters or conservation officials. The measure did pass on November 3 by a slight margin, but the DOI’s announcement on October 26 has complicated the endeavor to boost wolf numbers before it even begins.
The DOI’s statement justified delisting the wolves by saying that with more than 6,000 gray wolves now living in the contiguous United States, recovery efforts have “greatly exceeded” the goals that had been set forth by the agency.
One aspect that will make Prop. 114’s implementation easier is the fact that if the animal is not a protected species, there are fewer hoops to jump through with getting the permits to send them into the wild.
“So it’s an ironic benefit at the state level while we disagree with delisting wolves in the first place,” Rob Edward, president of the Rocky Mountain Wolf Action Fund, tells The Daily Sentinel.
While the paperwork might become easier without having to go through federal channels, a significant amount of money to help make the transition a success would no longer be available if the wolves aren’t on the endangered species list anymore. Edward tells the Sentinel that as much as 75 percent of the funding for the project was expected to come from the federal government. Although there might still be some federal money available, it isn’t as clear where the bulk of the funding will come from or how the program will proceed.
The Denver Gazette reports that Michael Robinson, a senior conservation advocate with the Center for Biological Diversity, says he does not believe that President-Elect Joe Biden’s incoming administration is likely to reverse the decision made by the current administration.


thescientist--2020-11-18--SynDevRx Announces Positive Data from Phase 1 Safety Trial of SDX-7320 in Late Stage Cancer Patients

SynDevRx , Inc. , a clinical-stage oncology company , has submitted results of its Phase 1 dose escalation safety study in late-stage cancer patients with progressive , metastatic solid tumors to the United States Food and Drug Administration ( FDA ) [ 1 ] .
The study ’ s primary endpoint was to establish the maximum tolerated dose and dosing schedule and the recommended Phase 2 dose for SDX-7320 , the company ’ s lead drug candidate for the treatment of metabolically sensitive cancers [ 2 ] .
Secondary and exploratory endpoints included analysis of anti-tumor efficacy and changes in @ @ @ @ @ @ @ study evaluated data from 32 patients , whose disease progression and new lesion formation were measured at intervals of every 2 months from the initiation of treatment .
Exploratory changes from baseline to metabolic hormones were measured , including leptin and adiponectin , as well as changes to insulin levels and insulin sensitivity ( HOMA-IR ) .
Exploratory changes from baseline to angiogenesis biomarkers bFGF , VEGF , and IGF-1 were also evaluated .
A total of 28 patients had at least one tumor burden assessment performed , of whom 21 ( 75 @ @ @ @ @ @ @ disease determination before leaving the study or experiencing progressive disease .
Of these 21 patients , the period of measurable stable disease averaged 85 days .
There were no objective partial or complete responses .
“ The results of our Phase 1 trial suggest that SDX-7320 may have potent anti-angiogenic activity , appears to induce favorable changes to insulin , leptin and adiponectin , and has a safety profile that supports future combination studies .
These data provide us with the scientific rationale for future clinical studies in tumors that are sensitive to @ @ @ @ @ @ @ ” said Brad Carver , President and CEO of SynDevRx .
“ Animal data we previously presented at the San Antonio Breast Cancer Symposium in 2019 showed that SDX-7320 attenuated the hyperglycemia and hyperinsulinemia caused by the PI3K inhibitor alpelisib , and showed synergistic tumor growth inhibition in mice .
Considering the aforementioned data together with this clinical data , we believe SDX-7320 could provide real benefit to breast cancer patients taking a PI3K inhibitor .
We expect to open enrollment for our upcoming clinical trial in metastatic ER+/Her2- breast cancer patients with @ @ @ @ @ @ @ next year , followed by additional trials focused on triple-negative breast cancer and prostate cancer , tumor types that are highly sensitive to systemic metabolic dysfunction.
” SynDevRx ’ s Phase 1 dose escalation study was designed to assess the safety and tolerability of SDX-7320 in patients with advanced refractory or late-stage solid tumors ( lung , colon , breast , rectal , pancreatic , appendiceal , carcinoid , cholangiocarcinoma , cervical , endometrial , hepatocellular , and urothelial cancers ) .
[ 3 ] Patients were a mean age of 66 years @ @ @ @ @ @ @ lines of treatment for their metastatic disease , on average .
SDX-7320 was administered subcutaneously at doses ranging from 1.7–65 mg/m2 and induced primarily mild side effects including fatigue , GI symptoms ( nausea , abdominal pain , diarrhea ) , and anemia .
The dose-limiting toxicity event , thrombocytopenia , was generally reversible without intervention and was observed only at the highest doses tested .
Results of the study suggest that the dose of SDX-7320 at 49 mg/m2 on a once every two weeks ( i.e.
, Q14D ) schedule may be @ @ @ @ @ @ @ ] SDX-7320 acts by inhibiting MetAP2 , a clinically validated target that appears to play a key role in tumor growth , metastasis , angiogenesis , and metabolic dysfunction .
“ Many solid tumor types are highly sensitive to dysregulated metabolic hormones , such as insulin , leptin , or adiponectin .
These hormones signal through known oncogenic pathways , like PI3K/Akt/mTOR or STAT3 .
Given the epidemic of metabolic syndrome in the world plus the frequency of tumors that are sensitive to metabolic hormones ( e.g.
, breast and prostate cancers ) @ @ @ @ @ @ @ clinical oncologists treat their cancer patients with concomitant , systemic metabolic dysfunction in combination with standard-of-care therapies , ” said James Shanahan , Co-Founder and Chief Business Officer of SynDevRx .
SynDevRx believes that SDX-7320 is the first drug being developed specifically for cancer patients with metabolic complications , such as obesity , diabetes , high blood glucose or HbA1c , pre-diabetes or insulin resistance .
For certain tumor types , metabolic hormones stimulate oncogenic pathways , making the cancer more aggressive and deadlier .
SDX-7320 acts by binding irreversibly to the target @ @ @ @ @ @ @ metabolic hormones , insulin , leptin and adiponectin .
Additionally , SDX-7320 inhibits the important angiogenic proteins bFGF and VEGF , and in preclinical studies , inhibited multiple cell cycle signaling pathways and reversed immune suppression within the tumor micro-environment .
SDX-7320 is being developed for use in combination with clinically indicated standard-of-care cancer therapies .

SynDevRx, Inc., a clinical-stage oncology company, has submitted results of its Phase 1 dose escalation safety study in late-stage cancer patients with progressive, metastatic solid tumors to the United States Food and Drug Administration (FDA) [1]. The study’s primary endpoint was to establish the maximum tolerated dose and dosing schedule and the recommended Phase 2 dose for SDX-7320, the company’s lead drug candidate for the treatment of metabolically sensitive cancers [2]. Secondary and exploratory endpoints included analysis of anti-tumor efficacy and changes in key angiogenic and metabolic biomarkers.
The study evaluated data from 32 patients, whose disease progression and new lesion formation were measured at intervals of every 2 months from the initiation of treatment. Exploratory changes from baseline to metabolic hormones were measured, including leptin and adiponectin, as well as changes to insulin levels and insulin sensitivity (HOMA-IR). Exploratory changes from baseline to angiogenesis biomarkers bFGF, VEGF, and IGF-1 were also evaluated. A total of 28 patients had at least one tumor burden assessment performed, of whom 21 (75%) had at least one stable disease determination before leaving the study or experiencing progressive disease. Of these 21 patients, the period of measurable stable disease averaged 85 days. There were no objective partial or complete responses.
“The results of our Phase 1 trial suggest that SDX-7320 may have potent anti-angiogenic activity, appears to induce favorable changes to insulin, leptin and adiponectin, and has a safety profile that supports future combination studies. These data provide us with the scientific rationale for future clinical studies in tumors that are sensitive to metabolic hormones, i.e., metabo-oncology,” said Brad Carver, President and CEO of SynDevRx. “Animal data we previously presented at the San Antonio Breast Cancer Symposium in 2019 showed that SDX-7320 attenuated the hyperglycemia and hyperinsulinemia caused by the PI3K inhibitor alpelisib, and showed synergistic tumor growth inhibition in mice. Considering the aforementioned data together with this clinical data, we believe SDX-7320 could provide real benefit to breast cancer patients taking a PI3K inhibitor. We expect to open enrollment for our upcoming clinical trial in metastatic ER+/Her2- breast cancer patients with a mutation in the PIK3CA gene early next year, followed by additional trials focused on triple-negative breast cancer and prostate cancer, tumor types that are highly sensitive to systemic metabolic dysfunction.”
About the Study:
SynDevRx’s Phase 1 dose escalation study was designed to assess the safety and tolerability of SDX-7320 in patients with advanced refractory or late-stage solid tumors (lung, colon, breast, rectal, pancreatic, appendiceal, carcinoid, cholangiocarcinoma, cervical, endometrial, hepatocellular, and urothelial cancers). [3] Patients were a mean age of 66 years old and had progressed following five prior lines of treatment for their metastatic disease, on average.
SDX-7320 was administered subcutaneously at doses ranging from 1.7–65 mg/m2 and induced primarily mild side effects including fatigue, GI symptoms (nausea, abdominal pain, diarrhea), and anemia. The dose-limiting toxicity event, thrombocytopenia, was generally reversible without intervention and was observed only at the highest doses tested. Results of the study suggest that the dose of SDX-7320 at 49 mg/m2 on a once every two weeks (i.e., Q14D) schedule may be appropriate for future studies. [3]
SDX-7320 acts by inhibiting MetAP2, a clinically validated target that appears to play a key role in tumor growth, metastasis, angiogenesis, and metabolic dysfunction. “Many solid tumor types are highly sensitive to dysregulated metabolic hormones, such as insulin, leptin, or adiponectin. These hormones signal through known oncogenic pathways, like PI3K/Akt/mTOR or STAT3. Given the epidemic of metabolic syndrome in the world plus the frequency of tumors that are sensitive to metabolic hormones (e.g., breast and prostate cancers), we believe that SDX-7320 could help clinical oncologists treat their cancer patients with concomitant, systemic metabolic dysfunction in combination with standard-of-care therapies,” said James Shanahan, Co-Founder and Chief Business Officer of SynDevRx.
About SDX-7320:
SynDevRx believes that SDX-7320 is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. SDX-7320 acts by binding irreversibly to the target enzyme MetAP2, triggering improvements in the metabolic hormones, insulin, leptin and adiponectin. Additionally, SDX-7320 inhibits the important angiogenic proteins bFGF and VEGF, and in preclinical studies, inhibited multiple cell cycle signaling pathways and reversed immune suppression within the tumor micro-environment. SDX-7320 is being developed for use in combination with clinically indicated standard-of-care cancer therapies.


thescientist--2020-11-18--The Scientist Speaks Podcast - Episode 11

Most infectious disease research focuses on the battle between host and pathogen .
While an individual ’ s abilities to @ @ @ @ @ are important , this process is only half of the story .
In this month @ @ @ @ @ from The Scientist ’ s Creative Services team spoke with David Schneider , professor of @ @ @ @ @ University , to learn why it is crucial to consider how organisms tolerate disease , @ @ @ @ @ maps the paths individuals take through infection and back to health .
The Scientist Speaks @ @ @ @ @ The Scientist ’ s Creative Services team .
Our podcast is by scientists and for @ @ @ @ @ , we will bring you the stories behind news-worthy molecular biology research .
This month @ @ @ @ @ MilliporeSigma .

Most infectious disease research focuses on the battle between host and pathogen. While an individual’s abilities to resist infection and combat microbes are important, this process is only half of the story.
In this month's episode, Niki Spahich from The Scientist’s Creative Services team spoke with David Schneider, professor of microbiology and immunology at Stanford University, to learn why it is crucial to consider how organisms tolerate disease, and to explore how he maps the paths individuals take through infection and back to health.
The Scientist Speaks is a podcast produced by The Scientist’s Creative Services Team. Our podcast is by scientists and for scientists. Once a month, we bring you the stories behind news-worthy molecular biology research. This month's episode is sponsored by MilliporeSigma.


thescientist--2020-11-18--Assay for Sickle Cell Anemia Is Repurposed to Diagnose COVID-19

In 1965 , the famous Indian filmmaker Satyajit Ray created a beloved fictional detective named Feluda .
In a series of short stories , the astute gumshoe tracks a vandal trying to destroy the ancient temples of India , busts a counterfeit medicine racket in Kathmandu , and cleans Bombay smugglers ’ clocks .
Inspired by the great analytical skills of the detective , researchers at the Delhi-based Council of Scientific and Industrial Research ( CSIR ) -Institute of Genomics and Integrative Biology have given their new CRISPR-based diagnostic for COVID-19 the affectionate nickname of Feluda ( short for FnCas9 @ @ @ @ @ @ @ TataMD Check , the commercial name of the test powered by Feluda , was launched on November 9 in India .
The test uses the CRISPR-Cas system to probe for genetic sequences specific to the SARS-CoV-2 virus in samples from nasal swabs or saliva applied to a paper strip .
Like the fictional Feluda , it is fast , accurate , and works in all manner of field settings , according to a preprint posted to medRxiv in September .
The regulatory agencies in India conducted an independent evaluation of the assay on @ @ @ @ @ @ @ highly accurate in detecting COVID-19 infections .
“ The combination of precision , speed , and affordability in this technology is remarkable , ” says Prashant Yadav , a healthcare supply-chain expert and senior fellow at the Center for Global Development in Washington , DC , a think tank largely supported by the Bill & Melinda Gates Foundation .
The Drugs Controller General of India approved Feluda for commercial use on September 19 , and in an October 22 advisory , the Indian Council of Medical Research approved its use by public and @ @ @ @ @ @ @ 500 rupees ( $ 6.75 US ) to make and process in the lab for a patient sample and gives results within an hour .
“ Once validated at large scale and commercial manufacturing issues are dealt with , it can become the mainstay of COVID-19 testing , not only in India but many other countries in the world who are seeking a fast , affordable , and precise test , ” says Yadav , who is not involved in the project .
India ’ s first reported case of COVID-19 was on @ @ @ @ @ @ @ on March 12.In the beginning of the pandemic , testing was limited to a few publicly funded laboratories in India .
Later on , it was extended to private labs .
Still , capacity is limited .
India currently tests only around 0.1 percent of its population of 1.4 billion each day , causing the country to rank among the lowest in the world on a per-capita basis .
The US has nearly as many tests per day—around 1.2 million , compared with India ’ s 1.5 million—but a population that is smaller @ @ @ @ @ @ @ Gautam Menon , a professor of physics and biology at Ashoka University and at the Institute of Mathematical Sciences in India who was not involved in the research .
“ I would think that we should test about 0.5 percent of our population every day , as an ideal , but we are testing more than ever before , ” he says .
Earlier this year , a team of researchers at the Pune-based biotech company MyLab Discovery Solutions developed a test kit—PathoDetect—for COVID-19 that returns results in 2.5 hours with 100 percent @ @ @ @ @ @ @ PCR test for the novel coronavirus made in India that was approved in the country .
It costs about $ 16 .
For PathoDetect , a significant limiting factor is the cost of the real-time PCR machine itself , which can be around $ 26,000 US .
Feluda , however , uses a paper strip to reveal results , similar to the readout of a pregnancy test .
Anyone who can run a normal PCR machine and follow a simple pipetting protocol can do this , says co-lead scientist Debojyoti Chakraborty .
Feluda @ @ @ @ @ @ @ or healthcare center that houses a simple PCR machine and its equipment and reagents are less expensive than PathoDetect ’ s are .
The assay has been tested on more than 2,000 samples .
It detected those who have SARS-CoV-2 , a measure of sensitivity , 96 percent of the time , while ruling out those who didn ’ t have the virus , a measure of its specificity , 98 percent of the time .
Feluda emerged out of “ serendipity , ” says Chakraborty .
For the past two-and-a-half years , @ @ @ @ @ @ @ been working on a Cas9 system that could detect the mutation in the gene that causes sickle cell anemia for point-of-care CRISPR diagnostics .
To test their approach , they traveled to far-flung healthcare centers in Chattisgarh state in India and collected saliva samples from people known to have sickle cell anemia as well as from potential silent carriers of the mutation .
As they were readying the publication of their results in January , COVID-19 hit , and they wondered if they could repurpose the technology to detect SARS-CoV-2 .
Starting right @ @ @ @ @ @ @ of graduate students and postdocs worked day and night , with some colleagues falling sick with the virus along the way .
By March , they had developed a prototype diagnostic , and in May , they licensed the technology to TATA Medical and Diagnostics Limited , which ushered it through regulatory approval .
Feluda works by first converting viral RNA from a sample to DNA , and then amplifying specific viral genes via PCR , during which it puts a biotin tag on the amplified products .
Following this , the sample @ @ @ @ @ @ @ with a fluorescently tagged FnCas9–guide RNA complex , which looks for these sequences from SARS-CoV-2 and hooks onto them , creating a larger complex of the fluorescent FnCas9 and biotin-labeled viral DNA sequence .
Then , the technician adds a buffer and dips a paper strip into the tube .
Gold nanoparticles on the paper recognize the fluorescent tag and the whole complex flows up the strip and gets deposited on a line of streptavidin , which interacts with the biotin label on the DNA .
The accumulation of the nanoparticles produces the @ @ @ @ @ @ @ of other CRISPR-based tests for COVID-19 , including one developed by MIT and Harvard University , and these employ Cas12 or Cas13 proteins to find the virus .
Harikrishnan Jayamohan , a research scientist at the University of Utah who was not involved in the work , says , “ If Feluda works on a large scale in India , this would be a good alternative to RT-PCR .
This would also be a big jump over antigen tests , which are widely-used , cheap , fast , and easy to use but @ @ @ @ @ @ @ 50 percent of India ’ s COVID-19 diagnostics are done through antigen testing .
“ Feluda is good in certain ways , ” says Rakesh Kumar Mishra , the director of Hyderabad-based CSIR-Centre for Cellular and Molecular Biology who was not involved in the Feluda research .
It will be particularly useful in remote places because Feluda can work with a simple PCR machine and that machine can be housed in rural healthcare center .
But the real value of a paper-strip test is when it can be used for self-testing or at @ @ @ @ @ @ @ is not ready for that yet .
“ This is a tough thing we ’ re fighting , ” says Mishra .
“ Any tool is a good tool .
”

ABOVE: Feluda-based detection of SARS-CoV-2
DR. DEBOJYOTI CHAKRABORTY’S LAB, CSIR-IGIB
In 1965, the famous Indian filmmaker Satyajit Ray created a beloved fictional detective named Feluda. In a series of short stories, the astute gumshoe tracks a vandal trying to destroy the ancient temples of India, busts a counterfeit medicine racket in Kathmandu, and cleans Bombay smugglers’ clocks. Inspired by the great analytical skills of the detective, researchers at the Delhi-based Council of Scientific and Industrial Research (CSIR)-Institute of Genomics and Integrative Biology have given their new CRISPR-based diagnostic for COVID-19 the affectionate nickname of Feluda (short for FnCas9 Editor Linked Uniform Detection Assay). TataMD Check, the commercial name of the test powered by Feluda, was launched on November 9 in India.
The test uses the CRISPR-Cas system to probe for genetic sequences specific to the SARS-CoV-2 virus in samples from nasal swabs or saliva applied to a paper strip. Like the fictional Feluda, it is fast, accurate, and works in all manner of field settings, according to a preprint posted to medRxiv in September. The regulatory agencies in India conducted an independent evaluation of the assay on patient samples and found Feluda to be highly accurate in detecting COVID-19 infections.
“The combination of precision, speed, and affordability in this technology is remarkable,” says Prashant Yadav, a healthcare supply-chain expert and senior fellow at the Center for Global Development in Washington, DC, a think tank largely supported by the Bill & Melinda Gates Foundation.
The Drugs Controller General of India approved Feluda for commercial use on September 19, and in an October 22 advisory, the Indian Council of Medical Research approved its use by public and private laboratories. The test costs about 500 rupees ($6.75 US) to make and process in the lab for a patient sample and gives results within an hour.
“Once validated at large scale and commercial manufacturing issues are dealt with, it can become the mainstay of COVID-19 testing, not only in India but many other countries in the world who are seeking a fast, affordable, and precise test,” says Yadav, who is not involved in the project.
India’s first reported case of COVID-19 was on January 30, and the first death on March 12.In the beginning of the pandemic, testing was limited to a few publicly funded laboratories in India. Later on, it was extended to private labs. Still, capacity is limited. India currently tests only around 0.1 percent of its population of 1.4 billion each day, causing the country to rank among the lowest in the world on a per-capita basis.
The US has nearly as many tests per day—around 1.2 million, compared with India’s 1.5 million—but a population that is smaller by a factor of four, explains Gautam Menon, a professor of physics and biology at Ashoka University and at the Institute of Mathematical Sciences in India who was not involved in the research. “I would think that we should test about 0.5 percent of our population every day, as an ideal, but we are testing more than ever before,” he says.
Earlier this year, a team of researchers at the Pune-based biotech company MyLab Discovery Solutions developed a test kit—PathoDetect—for COVID-19 that returns results in 2.5 hours with 100 percent accuracy. It was the first real-time PCR test for the novel coronavirus made in India that was approved in the country. It costs about $16. For PathoDetect, a significant limiting factor is the cost of the real-time PCR machine itself, which can be around $26,000 US.
Feluda, however, uses a paper strip to reveal results, similar to the readout of a pregnancy test. Anyone who can run a normal PCR machine and follow a simple pipetting protocol can do this, says co-lead scientist Debojyoti Chakraborty. Feluda can be performed at any diagnostic lab or healthcare center that houses a simple PCR machine and its equipment and reagents are less expensive than PathoDetect’s are.
The assay has been tested on more than 2,000 samples. It detected those who have SARS-CoV-2, a measure of sensitivity, 96 percent of the time, while ruling out those who didn’t have the virus, a measure of its specificity, 98 percent of the time.
From sickle cell anemia to COVID-19
Feluda emerged out of “serendipity,” says Chakraborty. For the past two-and-a-half years, he and his colleague Souvik Maiti had been working on a Cas9 system that could detect the mutation in the gene that causes sickle cell anemia for point-of-care CRISPR diagnostics. To test their approach, they traveled to far-flung healthcare centers in Chattisgarh state in India and collected saliva samples from people known to have sickle cell anemia as well as from potential silent carriers of the mutation.
As they were readying the publication of their results in January, COVID-19 hit, and they wondered if they could repurpose the technology to detect SARS-CoV-2.
Starting right away, Chakraborty says, his team of graduate students and postdocs worked day and night, with some colleagues falling sick with the virus along the way. By March, they had developed a prototype diagnostic, and in May, they licensed the technology to TATA Medical and Diagnostics Limited, which ushered it through regulatory approval.
Feluda works by first converting viral RNA from a sample to DNA, and then amplifying specific viral genes via PCR, during which it puts a biotin tag on the amplified products. Following this, the sample is incubated in the same PCR tube with a fluorescently tagged FnCas9–guide RNA complex, which looks for these sequences from SARS-CoV-2 and hooks onto them, creating a larger complex of the fluorescent FnCas9 and biotin-labeled viral DNA sequence. Then, the technician adds a buffer and dips a paper strip into the tube. Gold nanoparticles on the paper recognize the fluorescent tag and the whole complex flows up the strip and gets deposited on a line of streptavidin, which interacts with the biotin label on the DNA. The accumulation of the nanoparticles produces the visible signal.
There are a handful of other CRISPR-based tests for COVID-19, including one developed by MIT and Harvard University, and these employ Cas12 or Cas13 proteins to find the virus.
Harikrishnan Jayamohan, a research scientist at the University of Utah who was not involved in the work, says, “If Feluda works on a large scale in India, this would be a good alternative to RT-PCR. This would also be a big jump over antigen tests, which are widely-used, cheap, fast, and easy to use but are of very low sensitivity.” Nearly 50 percent of India’s COVID-19 diagnostics are done through antigen testing.
“Feluda is good in certain ways,” says Rakesh Kumar Mishra, the director of Hyderabad-based CSIR-Centre for Cellular and Molecular Biology who was not involved in the Feluda research. It will be particularly useful in remote places because Feluda can work with a simple PCR machine and that machine can be housed in rural healthcare center. But the real value of a paper-strip test is when it can be used for self-testing or at home, Yadav says, although Feluda is not ready for that yet.
“This is a tough thing we’re fighting,” says Mishra. “Any tool is a good tool.”
M. Azhar et al., “Rapid, accurate, nucleobase detection using FnCas9,” medRxiv, doi:10.1101/2020.09.13.20193581, 2020.


thescientist--2020-11-19--Expanding Cell Growth Capabilities

Expanding Cell Growth Capabilities

From basic research to clinical and industrial production , researchers need to prepare high-quality microbial or animal cell cultures .
@ @ @ @ @ and bioreactors are critical for optimizing and increasing cell growth to make influential research discoveries @ @ @ @ @ .
Download this ebook from Eppendorf to learn about

From basic research to clinical and industrial production, researchers need to prepare high-quality microbial or animal cell cultures. Culture shakers, incubators, and bioreactors are critical for optimizing and increasing cell growth to make influential research discoveries and produce vaccines and biomedicines.
Download this ebook from Eppendorf to learn about