Dear Readers:

When it comes to physical activities, have you concluded that you're not as young as you used to be? Maybe you were once a runner, and now the knees don't bend like they used to. Or perhaps you were a star athlete in high school, and now your star just isn't as bright. The body has gotten older, the joints stiffer, maybe it's even affecting your everyday life. It's a foe that sometimes rears its ugly head in mid-life; it's arthritis.

In the US, as many as 54 million people suffer from osteoarthritis (OA). The word comes from the Greek "osteon" meaning bone, and "itis" meaning inflammation. OA is the most common form of arthritis and occurs when the cartilage that cushions bones wears down over time. Joints can become painful, swollen, and difficult to move. The most commonly affected areas are knees, hands, hips, lower back, and neck.

Some supplements claim to ease arthritis pain, but do they work? Glucosamine, chondroitin, and curcumin (found in turmeric) are three dietary supplements we will explore. Glucosamine and chondroitin, often sold in combination, are two of the top-selling natural remedies for OA. In a meta-analysis of randomized controlled trials (the gold standard for research), Zhu et al. found that glucosamine was more effective than a sugar pill in alleviating joint stiffness. At the same time, chondroitin was better at improving pain and mobility. The analysis did not find enough studies to draw a conclusion about the combination therapy of the two (1).

In the 2019 treatment guidelines, the Arthritis Foundation and American College of Rheumatology gave a conditional recommendation of chondroitin sulfate for hand OA. However, the National Center for Complementary and Integrative Health says the evidence on glucosamine for OA is unclear, and chondroitin isn't helpful. Still, these supplements have not found to be harmful (2).

Another popular remedy for OA is curcumin, the ingredient in turmeric that has anti-inflammatory effects. In another meta-analysis Daily et al. concluded that curcumin, in addition to conventional medicine, may be useful in treating arthritis symptoms (3). In another study, curcumin was found to be as effective in treating arthritis of the knee as the drug diclofenac. However, this study was small and only lasted one month (4).

When it comes to your health, be an informed consumer. A little homework may be necessary before purchasing a supplement for arthritis symptoms. The following websites will help you make a sound decision:

Consult your doctor before beginning any dietary supplement.

Until next time, be healthy!

Dear Dietitian

References

https://www.health.harvard.edu/blog/curcumin-for-arthritis-does-it-really-work-2019111218290

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Dear Dietitian Are there dietary supplements that help with arthritis? - Kiowa County Press

Across America, the back-to-school season is nearly upon us. Yet for millions of children, that wont necessarily mean returning to their classrooms.

School administrators, public health officials and epidemiologists are still working to understand what it will take to make school campuses safe in the midst of the COVID-19 pandemic.

The health and safety of all in the school community is not something we can compromise on, said L.A. schools Supt. Austin Beutner, head of the second-largest district in the country. Our goal is to have students back in schools as soon as it is safe and appropriate to do so.

But what exactly does safe and appropriate mean?

The answer depends on the priorities, resources and risk tolerance in a particular community.

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Quite frankly, the context of COVID-19 transmission and spread is so different across communities that a one-size-fits-all solution is not appropriate, said Kenne Dibner, an education researcher at the National Academies of Sciences, Engineering, and Medicine who served as the staff director for a report on reopening schools that has been downloaded more than 300,000 times.

Dibner and other experts spoke to The Times about how to think through the complex, controversial and multi-pronged problem of reopening.

COVID-19 statistics are everywhere. All you need is a smartphone to see the number of people who have tested positive for the coronavirus, how fast it is spreading, how many ventilators are available in hospitals near you, and whether the number of deaths reported each day is rising or falling.

Despite the abundance of data, there is no magic number that automatically means its safe for schools to reopen.

We cannot offer zero risk, said Dr. Neha Nanda, the medical director of infection prevention at Keck Medicine of USC. The best we can do is combine a concoction of imperfect measures to come up with an optimal strategy.

For example, decision makers at L.A. Unified School District will pay special attention to the number of new cases per day and the proportion of coronavirus tests that come back positive as the two leading indicators of when we can consider bringing students back, Beutner said.

California guidelines require that a countys test positivity rate be no higher than 8% for two consecutive weeks in order for schools there to even consider reopening. As of Wednesday, the seven-day average positivity rate in L.A. County was 8.3%.

Beutner noted that the World Health Organization recommends keeping schools closed until the positive rate drops to 5%.

Having two weeks of less than 5% positivity seems a little difficult to achieve any time soon, unless we learn something more about the virus between then and now, Nanda said.

To help educators think through the health risks, Lauren Ancel Meyers, a professor of integrative biology at the University of Texas at Austin, created a tool that estimates how many kids and teachers would be likely to bring the coronavirus with them to campus if schools in their county were to reopen. Those estimates are based on the prevalence of the virus in the area and the size of the school, among other factors.

The tool is imperfect, since theres still so much uncertainty about how likely it is that a single student or teacher with the virus would infect others in the school. Researchers suspect that age makes a difference, though theyre not sure how much. Preventive measures in place at a school, such as the ability to social distance and adequate ventilation, matter too.

I am by no means for keeping schools closed, Ancel Meyers said. The point of doing these calculations is to provide information that can help deciders make the best decisions

Most of the debate is focused on the health risks of opening schools, but childrens health can suffer when schools are closed as well. Thats something decision-makers should keep in mind, according to a recent editorial published in the Journal of the American Medical Assn.

Weighing these competing health risks is a challenge, however. Compared with other types of data, the health risks associated with keeping schools closed are typically more diffuse, accrue over longer periods of time, and are more difficult to measure.

But that doesnt mean they dont exist.

Einstein said Not everything that counts can be counted, said Julie Donohue, a professor of health policy and management at the University of Pittsburgh and co-author of the JAMA editorial. We are massively experiencing that quote right now.

Schools provide an array of benefits to children and families in addition to education meals, physical and mental health services, support for students with learning difficulties and other special needs, and essential childcare that allows parents to work. Take these away and student health could suffer, Donohue said.

We need to ask ourselves, are we trying to maximize health outcomes, or are we trying to maximize COVID health outcomes, she said.

COVID-19 has not affected everyone equally, and school closures wont either.

Students from families with more advantages including parents who can work from home and access to high-speed internet connections will likely fare better with remote learning. Meanwhile, students who rely on school for meals and health services will be giving up more when school buildings are closed.

In addition, younger students, particularly those learning to read, are expected to get less out of virtual school than older children.

Teachers, administrators, public health workers, physicians, social workers and others should all be invited to offer their thoughts on whether to reopen schools. But the families who will feel the greatest impact of school closures must be at the decision-making table too, experts said.

The risk associated with coming back to schools really varies from family to family, and so we need to hear peoples real authentic experience, said Keisha Scarlett, chief of equity, partnerships and engagements for Seattle Public Schools and a contributor to the National Academies report.

Thats why Scarlett and her co-authors recommend that the decision of when and how to reopen schools be made by a broad coalition that can assess the resources a community has to support students staying at home, or safely returning to school.

Different communities rely on schools in different ways, and that needs to be considered in the process, said Dibner, director of the report.

It often feels as though weve been dealing with the coronavirus forever, but its been less than a year since it first infected humans, and scientists still have a lot to learn.

For instance, children under 18 make up just 5% of reported cases, which may be a sign that theyre more likely to carry the virus without developing symptoms. However, it is unclear how effective kids are at transmitting the virus, especially in a school setting.

Some countries in Europe have been able to reopen schools without seeing massive increases in case numbers. But when Israel reopened, cases spiked.

Learning from others, and learning from other countries, may be the best we can do right now, Nanda said. We have to be very conscientious about what is happening across the world and have an open mind.

We can also expect that circumstances here will change. Imagine the arrival of a COVID-19 test that worked like a pregnancy test, which would enable students and teachers to painlessly test themselves weekly or even daily.

Or perhaps a new treatment will be found that would make the virus less deadly. That would be a game-changer, Ancel Meyers said.

I wouldnt be respecting the virus if I said there wasnt more to learn, Nanda said. This thing has taught us humility very well.

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What is necessary to assure school safety amid COVID-19? - Los Angeles Times

Cheryl Schneider was leaving the checkout counter at her local Target Wednesday when she saw them.

Two men, just a few feet away from her, their faces completely exposed.

How about wearing your mask? said Schneider, 66. Its required.

I am, one of the men said, smiling and pointing at his chin. His face covering hung like a silly beard, protecting no one.

Idiot! said Schneiders daughter, Gabrielle, 33.

It wasnt the New Yorkers first such exchange. She likes using the catchphrase mask it or casket when she sees people ignoring the rules.

Ive been cursed at, yelled at, called names, says Schneider, a public relations professional. But I dont care.

Most of the people she sees without a mask?

Men.

Even as masks have become a part of our daily pandemic uniform and are required in all indoor and non-socially distanced outdoor spaces in New Jersey recent surveys show men are less likely to say they wear them all the time, and more likely to say they dont wear them at all.

A Gallup survey of 3,615 adults age 18 and older conducted June 29 to July 5 found that 20% of men said they never wear a mask outside the home, compared with 8% of women. Men were also less likely to say they intend to wear face coverings in a spring survey of 2,459 people in the United States from the Mathematical Sciences Research Institute in Berkeley, California and Middlesex University in London.

Men more than women believe that they will be relatively unaffected by the disease, researchers said in their May report. This is particularly ironic because official statistics show that actually the coronavirus (COVID-19) impacts men more seriously than women.

People lining up to buy beach badges in Belmar in May. Outdoor scenes aren't always so mask-compliant and not every state mandates that masks be worn indoors. Patti Sapone | NJ Advance Media for NJ.com

Why would men behave as if being a man equates to some kind of coronavirus immunity?

Its called maskulinity with a K, says Yasemin Besen-Cassino, a sociologist at Montclair State University.

That is a part of masculine identity and how we raise men, she says. Admitting this is something that can threaten your health is in direct conflict with how we assign masculinity.

This is also why men are less likely to get regular check-ups at the doctor and more likely to engage in risky behavior, Besen-Cassino says.

People men included have used masks to express their personal sense of style, team allegiances and New Jersey pride (Gov. Phil Murphy wore one that advertised his Parkway exit, 109). But in the May survey, men were more likely than women to agree that masks are shameful, not cool, a sign of weakness and a stigma, researchers said.

Of course, that assumes masks are intended to protect the wearer. On the contrary, we mainly wear them to shield others from getting COVID-19 from us, whether or not we have contracted the virus or know we have it.

Various stages of mask-wearing (and the absence of masks) on display at the pedestrian plaza on Jersey City's Newark Avenue in July. Aristide Economopoulos | NJ Advance Media for NJ.com

We raise women to be more caring and more susceptive to their environment, Besen-Cassino says. Wearing a mask is caring about other people and making sure others are okay.

The COVID-19 Consortium for Understanding the Publics Policy Preferences Across States surveyed 19,058 people across the country from July 10 to 26. The survey showed that 77% of women said they had followed the recommendation to wear a mask outside the home very closely, compared with 69% of men, says Katya Ognyanova, a professor of communication at Rutgers University in New Brunswick. The consortium is a joint project of Rutgers, Harvard, Northeastern and Northwestern universities.

In public health we work really hard to work on behavior change, says Rosie Frasso, director of public health at Thomas Jefferson University in Philadelphia, which operates medical centers in South Jersey. We try and understand the role of gender ... weve really screwed up with the messaging around this as a country.

For some, being outside has become a signal that masks are not necessary.Aristide Economopoulos | NJ Advance Media for NJ.com

An early aversion to masks was on full display with government leaders, including President Donald Trump and Vice President Mike Pence, chair of the White House Coronavirus Task Force. But even off TV screens, Frasso has anecdotally noticed gender differences in mask wearing.

The data on COVID show that men with COVID do far worse than women, she says. They should be extra motivated to avoid it.

Women are more likely to embrace masks because of an approach Frasso likens to putting on an oxygen mask before helping others on a plane.

Women are in lots of ways more responsible about health and health behavior than men because they end up being the organizers of health care for families, she says.

Its a pattern weve seen before.

Women adopted seatbelt use more readily than men, and that was a very similar debate, Frasso says.

For the most part, New Jersey's mask mandate can take the gendered "choice" out of mask wearing. Pictured: Cranford in July.Aristide Economopoulos | NJ Advance Media

Women readily see the connections between community and self, says Noah Kass, a psychotherapist and clinical director for NY Health Hypnosis and Integrative Therapy in Manhattan.

Men are more in touch with their ego they almost put themselves outside of their community and see that as a source of pride ... certainly the president doesnt help.

Men are more likely to be in denial about health problems, says Melinda Hall, director of the gender studies program at Stetson University in DeLand, Florida. But that kind of denial can also be seen in American culture at large, which upholds the myth that to be human is to work constantly and somehow not get sick. The health crisis, by keeping many at home, has often triggered a reassessment of round-the-clock productivity.

Autonomy and independence are really more of a fiction than anything, Hall says of the rugged individualist identity associated with America. Women are doing the kinds of work that highlights our interdependence.

Women wearing masks at the Haskell Invitational at Monmouth Park in July. It is women who often manage health care for their entire family.Andrew Mills | NJ Advance Media for NJ.com

How can officials cut down on gender-based mask avoidance? One solution can be found in measures that are already in effect in New Jersey and across the country. The May survey on mask use found that the disparity between women and men when it came to intentions about wearing face coverings almost disappears in places where they are mandatory.

A statewide New Jersey mask mandate applying to outdoor spaces went into effect July 8, expanding on the earlier mandate for indoor spaces. Though its clear that not everyone is wearing a mask outside when they arent social distancing, the COVID-19 Consortium survey found that 82% of New Jerseyans surveyed (of a total 388) said they followed mask recommendations very closely.

By comparison, of 254 people surveyed in South Dakota, which has no statewide mask mandate, just 37% said they did the same, and 21% said they followed guidelines to wear face coverings not at all closely.

The Gallup survey found that women (54%), Northeasterners (54%), people 55 and up (47%) and those with annual household incomes under $36,000 (51%) were among the top groups to say they always wear masks outside the home.

President Donald Trump wears a mask July 27 while touring a lab that makes components for a potential COVID-19 vaccine in Morrisville, North Carolina. For months after the CDC recommended them, Trump did not wear a mask.Jim Watson | AFP via Getty Images

But mask analysis isnt limited to gender, age, location and income. The COVID-19 Consortium found Asian respondents (85%) were most likely to say they wore a mask outside the home, echoing the example of mask-wearing cultures found in Asian countries. African American respondents (81%) followed, along with Hispanic respondents (80%). White mask wearers came in at 70%.

Looking at political affiliation, Democrats (84%) were most likely to say they closely follow guidelines to wear masks, while Republicans were least likely (64%). Democrats (92%) were also most likely to say masks are effective in preventing COVID-19 infection, and Republicans were least likely (76%).

President Trump, the most visible Republican, did not wear face coverings at public events for months after the Centers for Disease Control and Prevention recommended masks, and retweeted messages implying that former Vice President Joe Biden looked weak by wearing them. Trump also told told a reporter wearing a mask that he must want to be politically correct.

The president has since reversed course, wearing a mask in public for the first time in July at Walter Reed National Military Medical Center. He later tweeted a photo of himself in his presidential face covering, saying that wearing masks is considered patriotic.

People wore gauze masks during the 1918 flu pandemic, when putting one on was equated to supporting the war effort. National Archives and Records Administration/public domain

Trump deciding to wear a mask several months into the pandemic is like showing up to a baby shower with condoms, says Dr. Niket Sonpal, professor of clinical medicine at Touro College of Osteopathic Medicine in New York. Its too late.

The politicization of masks can transcend gender differences, as seen in Karen videos that depict middle-aged white women vehemently refusing to wear the face coverings. In June, when staff at a California Trader Joes confronted a woman for not wearing a mask, she proceeded to thrown down her cart and yell Democratic pigs! at people in the store. In July, a woman in Arizona filmed herself dismantling an entire mask display in Target because she disapproved. These anti-mask actors often claim that it is their right to flout store policies or state mandates by going without a mask.

A century ago, masks were routinely associated with patriotism and heroism. In the 1918 flu pandemic, putting on gauze masks to guard against infection was likened to soldiers overseas wearing gas masks during World War I, says Katie Foss, professor of media studies at Middle Tennessee State University.

If we think about the Spanish Flu, most of the messages we got about disease at that time were underscored by war discourse, says Foss, author of the forthcoming book Constructing the Outbreak: Media in Epidemics and Collective Memory (September, University of Massachusetts Press).

We have this switch from wearing a mask is a masculine thing, we moved away from that, Foss says, calling todays mask a loaded symbol.

In one survey, men were more likely to associate masks with weakness.Aristide Economopoulos | NJ Advance Media for NJ.com

While hand-washing may be second nature, those gauze masks from 1918 do not live in the public memory of 2020.

That fact that we dont have a cultural norm around mask-wearing makes this much more difficult, says Leslie Kantor, chair of the department of urban-global public health at Rutgers in Newark.

Still, that doesnt mean popular thinking about masks cant be reprogrammed.

We have a fast-moving epidemic and peoples personal habits are slow to change, Kantor says. We can change the associations with these prevention objects. We never stopped telling people how to prevent HIV and STDs and pregnancy you have to keep going.

Thank you for relying on us to provide the journalism you can trust. Please consider supporting NJ.com with a voluntary subscription.

Amy Kuperinsky may be reached at akuperinsky@njadvancemedia.com. Send a coronavirus tip here.

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Women in masks, men in denial: Why some say they wont cover up to fight COVID-19 - NJ.com

Our panel of medical and health experts will give you practical pointers on Covid-19 prevention such as:

Join the Mims Medical Lounge brought to you by TimesLIVE, as our panel of experts discuss how to protect your family from Covid-19.

The panel of experts include:

Dr Martin de Villiers (doctor of family medicine, university lecturer and medical director of Medwell SA, which specialises in home-based care)Dr Zimbini Ogle (clinical psychologist leading Impilo yeAfrica. With an MA in Clinical Psychology and PhD in Psychiatry, Dr Ogle treats common mental disorders, depression and anxiety disorders)Dr Maria Christodoulou (medical practitioner and an expert in integrative medicine. Dr Christodoulou specialises in coaching individuals to reclaim their health, align with their purpose, and liberate their full potential)Annelie Smith (registered dietitian with extensive experience in private practice and a specialty in nutrigenomics and functional nutrition. Smith heads up mentorship for 3X4 Genetics)Jani Greeff (creative consultant, songwriter, director and playwright. Greeff is a mother to a toddler and wife of musician husband Pierre of Die Heuwels Fantasties)

Date: Tuesday, August 11 2020Time: 4pm

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FREE WEBINAR | Join the Mims Medical Lounge on how to protect your family from Covid-19 - TimesLIVE

Sites of vulnerability in SARS-CoV-2

Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool in treating coronavirus disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell. A subset of antibodies was able to neutralize the virus. Competition and electron microscopy studies showed that these antibodies target diverse epitopes on the spike, with the two most potent targeting the domain that binds the host receptor.

Science, this issue p. 643

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.

The rapid emergence of three novel pathogenic human coronaviruses in the past two decades has caused major concerns. The latest, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for >3 million infections and 230,000 deaths worldwide as of 1 May 2020 (1). Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is characterized by mild, flu-like symptoms in most patients. However, severe cases can present with bilateral pneumonia that may rapidly deteriorate into acute respiratory distress syndrome (2). With high transmission rates and no proven curative treatment available, health care systems are severely overwhelmed, and stringent public health measures are in place to prevent infection. Safe and effective treatment and prevention measures for COVID-19 are urgently needed.

During the outbreak of the first severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), plasma of recovered patients containing neutralizing antibodies (NAbs) was used as a safe and effective treatment option to decrease viral load and to reduce mortality in severe cases (3, 4). Recently, a small number of COVID-19 patients treated with convalescent plasma showed clinical improvement and a decrease in viral load (5). An alternative treatment strategy would be to administer purified monoclonal antibodies (mAbs) with neutralizing capacity. mAbs can be thoroughly characterized in vitro and expressed in large quantities. In addition, because of the ability to control dosing and composition, mAb therapy has improved efficacy over convalescent plasma treatment and prevents the potential risks of antibody-dependent enhancement (ADE) from non-neutralizing or poorly neutralizing Abs present in plasma that consists of a polyclonal mixture (6). Recent studies with patients infected with the Ebola virus highlight the superiority of mAb treatment over convalescent plasma treatment (7, 8). Moreover, mAb therapy has been proven safe and effective against influenza virus, rabies virus, and respiratory syncytial virus (RSV) (911).

The main target for NAbs on coronaviruses is the spike (S) protein, a homotrimeric glycoprotein that is anchored in the viral membrane. Recent studies have shown that the S protein of SARS-CoV-2 bears considerable structural homology to that of SARS-CoV, consisting of two subdomains: the N-terminal S1 domain, which contains the N-terminal domain (NTD) and the RBD for the host cell receptor angiotensin-converting enzyme-2 (ACE2), and the S2 domain, which contains the fusion peptide (12, 13). Similar to other viruses containing class 1 fusion proteins (e.g., HIV-1, RSV, and Lassa virus), the S protein undergoes a conformational change and proteolytic cleavage upon host cell receptor binding from a prefusion to a postfusion state, enabling merging of viral and target cell membranes (14, 15). When expressed as recombinant soluble proteins, class 1 fusion proteins generally have the propensity to switch to a postfusion state. However, most NAb epitopes present in the prefusion conformation (1618). The recent successes of isolating potent NAbs against HIV-1 and RSV using stabilized prefusion glycoproteins reflect the importance of using the prefusion conformation for isolating and mapping mAbs against SARS-CoV-2 (19, 20).

Early efforts at obtaining NAbs focused on reevaluating SARS-CoVspecific mAbs isolated after the 2003 outbreak that might cross-neutralize SARS-CoV-2 (21, 22). Although two mAbs were described to cross-neutralize SARS-CoV-2, most SARS-CoV NAbs did not bind SARS-CoV-2 S protein or neutralize SARS-CoV-2 virus (12, 2123). More recently, the focus has shifted from cross-neutralizing SARS-CoV NAbs to the isolation of new SARS-CoV-2 NAbs from recovered COVID-19 patients (2428). S protein fragments containing the RBD have yielded multiple NAbs that can neutralize SARS-CoV-2 by targeting different RBD epitopes (2428). In light of the rapid emergence of escape mutants in the RBD of SARS-CoV and MERS, monoclonal NAbs targeting epitopes other than the RBD are a valuable component of any therapeutic antibody cocktail (29, 30). Indeed, therapeutic antibody cocktails with a variety of specificities have been used successfully against Ebola virus disease (7) and are being tested widely in clinical trials for HIV-1 (31). NAbs targeting non-RBD epitopes have been identified for SARS-CoV and MERS, supporting the rationale for sorting mAbs using the entire ectodomain of the SARS-CoV-2 S protein (32). In addition, considering the high sequence identity between the S2 subdomains of SARS-CoV-2 and SARS-CoV, using the complete S protein ectodomain instead of only the RBD may allow the isolation of mAbs that cross-neutralize different -coronaviruses (33). In an attempt to obtain mAbs that target both RBD and non-RBD epitopes, we set out to isolate mAbs using the complete prefusion S protein ectodomain of SARS-CoV-2.

We collected a single blood sample from three polymerase chain reactionconfirmed SARS-CoV-2infected individuals (COSCA1, COSCA2, and COSCA3) ~4 weeks after symptom onset. COSCA1 (a 47-year-old male) and COSCA2 (a 44-year-old female) showed symptoms of an upper respiratory tract infection and mild pneumonia, respectively (Table 1). Both remained in home isolation during the course of COVID-19 symptoms. COSCA3, a 69-year-old male, developed a severe pneumonia and became respiratory insufficient 1.5 weeks after symptom onset, requiring admission to the intensive care unit for mechanical ventilation. To identify S proteinspecific antibodies in the sera obtained from all three patients, we generated soluble, prefusion-stabilized S proteins of SARS-CoV-2 using stabilization strategies previously described for S proteins of SARS-CoV-2 and other -coronaviruses (Fig. 1A) (12, 34). As demonstrated by the size-exclusion chromatography trace, SDSpolyacrylamide gel electrophoresis (PAGE), and blue native PAGE, the resulting trimeric SARS-CoV-2 S proteins were of high purity (fig. S1, A and B). Sera from all patients showed strong binding to the S protein of SARS-CoV-2 in an enzyme-linked immunosorbent assay (ELISA), with end-point titers of 13,637, 6133, and 48,120 for COSCA1, COSCA2, and COSCA3, respectively (Fig. 1B), and showed cross-reactivity to the S protein of SARS-CoV (fig. S1C). COSCA1, COSCA2, and COSCA3 had varying neutralizing potencies against SARS-CoV-2 pseudovirus, with 50% inhibition of virus infection (ID50) values of 383, 626, and 7645, respectively (Fig. 1C), and similar activities against authentic virus (fig. S1D). In addition, all sera showed cross-neutralization of SARS-CoV pseudovirus and authentic SARS-CoV virus, albeit with low potency (fig. S1, E and F). The potent S proteinbinding and -neutralizing responses observed for COSCA3 are consistent with earlier findings showing that severe disease is associated with a strong humoral response (35). On the basis of these strong serum binding and neutralization titers, we sorted SARS-CoV-2 S proteinspecific B cells for mAb isolation from COSCA1, COSCA2, and COSCA3.

(A) (Top) Schematic overview of the authentic SARS-CoV-2 S protein with the signal peptide shown in blue and the S1 (red) and S2 (yellow) domains separated by a furin-cleavage site (RRAR; top). (Bottom) Schematic overview of the stabilized prefusion SARS-CoV-2 S ectodomain, where the furin cleavage site is replaced with a glycine linker (GGGG), two proline mutations are introduced (K986P and V987P), and a trimerization domain (cyan) preceded by a linker (GSGG) is attached. (B) Binding of sera from COSCA1, COSCA2, and COSCA3 to prefusion SARS-CoV-2 S protein as determined by ELISA. The mean values and SDs of two technical replicates are shown. (C) Neutralization of SARS-CoV-2 pseudovirus by heat-inactivated sera from COSCA1, COSCA2, and COSCA3. The mean and SEM of at least three technical replicates are shown. The dotted line indicates 50% neutralization.

Peripheral blood mononuclear cells were stained dually with fluorescently labeled prefusion SARS-CoV-2 S proteins and analyzed for the frequency and phenotype of specific B cells by flow cytometry (Fig. 2A and fig S2). The analysis revealed a frequency ranging from 0.68 to 1.74% of S proteinspecific B cells (S-AF647+, S-BV421+) among the total pool of B cells (CD19+Via-CD3CD14CD16), (Fig. 2B). These SARS-CoV-2 S proteinspecific B cells showed a predominant memory (CD20+CD27+) and plasmablasts/plasma cells (PBs/PCs) (CD20CD27+CD38+) phenotype. We observed a threefold higher percentage of PBs/PCs for SARS-CoV-2 S proteinspecific B cells compared with total B cells (P = 0.034), indicating an enrichment of specific B cells in this subpopulation (Fig. 2C). COSCA3, who experienced severe symptoms, showed the highest frequency of PBs/PCs in both total (34%) and specific (60%) B cells (Fig. 2C and fig. S2). As expected, the SARS-CoV-2 S proteinspecific B cells were enriched in the immunoglobulin Gpositive (IgG+) and IgM/IgG (most likely representing IgA+) B cell populations, although a substantial portion of the specific B cells were IgM+, particularly for COSCA3 (Fig. 2D).

(A) Representative gates of SARS-CoV-2 S proteinspecific B cells shown for a nave donor (left panel) or COSCA1 (middle left panel). Each dot represents a B cell. The gating strategy to identify B cells is shown in fig. S2. From the total pool of SARS-CoV-2 S proteinspecific B cells, CD27+CD38 memory B cells (Mem B cells; blue gate) and CD27+CD38+ B cells were identified (middle panel). From the latter gate, PBs/PCs (CD20; red gate) could be identified (middle right panel). SARS-CoV-2 S proteinspecific B cells were also analyzed for their IgG or IgM isotype (right panel). (B) Frequency of SARS-CoV-2 S proteinspecific B cells in total B cells, Mem B cells, and PBs/PCs. Symbols represent individual patients, as shown in (D). (C) Comparison of the frequency of Mem B cells (CD27+CD38) and PB/PC cells (CD27+CD38+CD20) between the specific (SARS-CoV2 S++) and nonspecific B cells (gating strategy is shown in fig. S2). Symbols represent individual patients, as shown in (D). Statistical differences between two groups were determined using paired t test (*P = 0.034). (D) Comparison of the frequency of IgM+, IgG+, and IgMIgG B cells in specific and nonspecific compartments. Bars represent means; symbols represent individual patients.

SARS-CoV-2 S proteinspecific B cells were subsequently single-cell sorted for sequencing and mAb isolation. In total, 409 heavy chain (HC) and light chain (LC) pairs were obtained from the sorted B cells of the three patients (137, 165, and 107 from COSCA1, COSCA2, and COSCA3, respectively), of which 323 were unique clonotypes. Clonal expansion occurred in all three patients (Fig. 3A) but was strongest in COSCA3, where it was dominated by HC variable (VH) regions VH3-7 and VH4-39 (34 and 32% of SARS-CoV-2 S proteinspecific sequences, respectively). Even though substantial clonal expansion occurred in COSCA3, the median somatic hypermutation (SHM) was 1.4%, with similar SHM in COSCA1 and COSCA2 (2.1 and 1.4%, respectively) (Fig. 3B). These SHM levels are similar to those observed in response to infection with other respiratory viruses (36).

(A) Maximum-likelihood phylogenetic tree of 409 isolated paired B cell receptor HCs. Each color represents sequences isolated from different patients (COSCA1, COSCA2, and COSCA3). (B) Violin plot showing SHM levels (%; nucleotides) per patient. The dot represents the median SHM percentage. (C) Distribution of CDRH3 lengths in B cells from COSCA1, COSCA2, and COSCA3 (purple, n = 323) versus a representative nave population from three donors (cyan, n = 9.791.115) (37). (D) Bar graphs showing the mean ( SEM) VH gene usage (%) in COSCA1, COSCA2, and COSCA3 (purple, n = 323) versus a representative nave population (cyan, n = 363,506,788). The error bars represent the variation between different patients (COSCA1, COSCA2, and COSCA3) or nave donors (37). Statistical differences between two groups were determined using unpaired t tests (with HolmSidak correction for multiple comparisons, adjusted P values: *P < 0.05; **P < 0.01; ***P < 0.001).

A hallmark of antibody diversity is the heavy chain complementarity-determining region 3 (CDRH3). Because the CDRH3 is composed of V, D, and J gene segments, it is the most variable region of an antibody in terms of both amino acid composition and length. The average length of CDRH3 in the nave human repertoire is 15 amino acids (37), but for a subset of influenza virus and HIV-1 broadly neutralizing antibodies, long CDRH3 regions of 20 to 35 amino acids are crucial for high-affinity antigenantibody interactions (38, 39). Even though the mean CDRH3 length of isolated SARS-CoV-2 S proteinspecific B cells did not differ substantially from that of a nave population (37), we observed a significant difference in the distribution of CDRH3 length (two-sample KolmogorovSmirnov test, P = 0.006) (Fig. 3C). This difference in CDRH3 distribution can largely be attributed to an enrichment of longer (~20 amino acid) CDRH3s, leading to a bimodal distribution as opposed to the bell-shaped distribution that was observed in the nave repertoire (Fig. 3C and fig. S3).

Next, to determine SARS-CoV-2specific signatures in B cell receptor repertoire usage, we compared ImmunoGenetics (IMGT) databaseassigned unique germline V regions from the sorted SARS-CoV-2 S proteinspecific B cells with the well-defined extensive germline repertoire in the nave population (Fig. 3D) (37). Multiple VH genes were enriched in COSCA1, COSCA2, and COSCA3 compared with the nave repertoire, including VH3-33 (P = 0.009) and VH1-24 (P < 0.001) (Fig. 3D). Even though the enrichment of VH1-69 was not significant (P > 0.05), it should be noted that an enrichment of VH1-69 has been shown in response to a number of other viral infections, including influenza virus, hepatitis C virus, and rotavirus (40), and an enrichment of VH3-33 was observed in response to malaria vaccination, whereas the enrichment of VH1-24 appears to be specific for COVID-19 (Fig. 3D) (41). By contrast, VH4-34 (P > 0.05) and VH3-23 (P = 0.018) were substantially underrepresented in SARS-CoV-2specific sequences compared with the nave population. Although usage of most VH genes was consistent between COVID-19 patients, VH3-30-3 and VH4-39 in particular showed considerable variability. Thus, upon SARS-CoV-2 infection, the S protein recruits a subset of B cells from the nave repertoire enriched in specific VH segments and CDRH3 domains.

Subsequently, all HC and LC pairs were transiently expressed in human embryonic kidney (HEK) 293T cells and screened for binding to SARS-CoV-2 S protein by ELISA. A total of 84 mAbs that showed high-affinity binding were selected for small-scale expression in HEK 293F cells and purified (table S1). We obtained few S proteinreactive mAbs from COSCA3, possibly because most B cells from this individual were IgM+, whereas cloning into an IgG backbone nullified avidity contributions to binding and neutralization present in the serum. To gain insight in the immunodominance of the RBD as well as its ability to cross-react with SARS-CoV, we assessed the binding capacity of these mAbs to the prefusion S proteins and the RBDs of SARS-CoV-2 and SARS-CoV using ELISA. Of the 84 mAbs tested, 32 (38%) bound to the SARS-CoV-2 RBD (Fig. 4, A and B), with seven mAbs (22%) showing cross-binding to SARS-CoV RBD (fig. S4A). We also observed 33 mAbs (39%) that bound strongly to SARS-CoV-2 S but did not bind the RBD, of which 10 mAbs (30%) also bound to the S protein of SARS-CoV (Fig. 4, A and B). Notably, some mAbs that bound very weakly to soluble SARS-CoV-2 S protein in ELISA showed strong binding to membrane-bound S protein, implying that their epitopes are presented poorly on the stabilized soluble S protein or that avidity is important for their binding (table S1). Surface plasmon resonance (SPR) assays confirmed binding of 77 mAbs to S protein and 21 mAbs to the RBD with binding affinities in the nanomolar to picomolar range (table S1).

(A) Bar graph depicting the binding of mAbs from COSCA1 (blue), COSCA2 (red), and COSCA3 (yellow) to SARS-CoV-2 S protein (dark shading) and SARS-CoV-2 RBD (light shading) as determined by ELISA. Each bar indicates the representative area under the curve (AUC) of the mAb indicated below from two experiments. The gray area represents the cutoff for binding (AUC = 1). The maximum concentration of mAb tested was 10 g/ml. (B) Scatter plot depicting the binding of mAbs from COSCA1, COSCA2, and COSCA3 [see (C) for color coding] to SARS-CoV-2 S protein and SARS-CoV-2 RBD as determined by ELISA. Each dot indicates the representative AUC of a mAb from two experiments. (C) Midpoint neutralization concentrations (IC50) of SARS-CoV-2 pseudovirus (left) or authentic SARS-CoV-2 virus (right). Each symbol represents the IC50 of a single mAb. For comparability, the highest concentration was set to 10 g/ml, although the actual start concentration for the authentic virus neutralization assay was 20 g/ml. The IC50s for pseudotyped and authentic SARS-CoV-2 virus of a selection of potently neutralizing RBD and non-RBDspecific mAbs (with asterisk) are shown in the adjacent table. Colored shading indicates the most potent mAbs from COSCA1, COSCA2, and COSCA3.

All 84 mAbs were subsequently tested for their ability to block infection. A total of 19 mAbs (23%) inhibited SARS-CoV-2 pseudovirus infection with varying potencies (Fig. 4C) and, of these, 14 (74%) bound the RBD. Seven of the 19 mAbs could be categorized as potent neutralizers [median inhibitory concentration (IC50) < 0.1 g/ml], six as moderate neutralizers (IC50 = 0.1 to 1 g/mL), and six as weak neutralizers (IC50 = 1 to 10 g/ml). With an IC50 of 0.008 g/ml, the RBD-targeting antibodies COVA1-18 and COVA2-15 in particular were unusually potent. However, they were quite different in other aspects, such as their HC V gene usage (VH3-66 versus VH3-23), LC usage (VL7-46 versus VK2-30), HC sequence identity (77%), and CDRH3 length (12 versus 22 amino acids). Seventeen of the mAbs also interacted with the SARS-CoV S and RBD proteins and two of these cross-neutralized the SARS-CoV pseudovirus (IC50 = 2.5 g/ml for COVA1-16 and 0.61 g/ml for COVA2-02; fig. S4B), with COVA2-02 being more potent against SARS-CoV than against SARS-CoV-2. Next, we assessed the ability of the 19 mAbs to block infection of authentic SARS-CoV-2 virus (Fig. 4C and fig. S4C). Although previous reports suggested a decrease in neutralization sensitivity of primary SARS-CoV-2 compared with pseudovirus (25, 27, 28), we observed very similar potencies for seven of the 19 NAbs, including the most potent NAbs (IC50 = 0.007 and 0.009 g/ml for COVA1-18 and COVA2-15, respectively; Fig. 4C). NAbs COVA1-18, COVA2-04, COVA2-07, COVA2-15, and COVA2-39 also showed strong competition with ACE2 binding, illustrating that blocking ACE2 binding is their likely mechanism of neutralization (fig. S4D). The RBD-targeting mAb COVA2-17, however, showed incomplete competition with ACE2. This corroborates previous observations that the RBD encompasses multiple distinct antigenic sites, some of which do not involve blocking of ACE2 binding (23, 25, 26). The non-RBD NAbs all bear substantially longer CDRH3s compared with RBD NAbs (fig. S4E), suggesting a convergent, CDRH3-dependent contact between antibody and epitope.

To identify and characterize the antigenic sites on the S protein and their interrelationships, we performed SPR-based cross-competition assays using S protein, followed by clustering analysis. We note that competition clusters do not necessarily equal epitope clusters but the analysis can provide clues as to the relationship between mAb epitopes. We identified 11 competition clusters, of which nine contained more than one mAb and two contained only one mAb (clusters X and XI; Fig. 5A and fig. S5). All nine multiple-mAb clusters included mAbs from at least two of the three patients, emphasizing that these clusters represent common epitopes targeted by the human humoral immune response during SARS-CoV-2 infection. Three clusters included predominantly RBD-binding mAbs (clusters I, III, and VII), with cluster I forming two subclusters. These three clusters were confirmed by performing cross-competition experiments with soluble RBD instead of complete S protein (fig. S5B). Four clusters (V, VI, XIII, and IX) included predominantly mAbs that did not interact with RBD, and clusters II, IV, X, and XI consisted exclusively of non-RBD mAbs. mAbs with diverse phenotypes (e.g., RBD and non-RBDbinding mAbs) merged together in multiple clusters, suggesting that these mAbs might target epitopes bridging the RBD and non-RBD sites or that they sterically interfere with each others binding as opposed to binding to overlapping epitopes. Although clusters II, V, and VIII contained only mAbs incapable of neutralizing SARS-CoV-2, clusters I, III, IV, VI, and VII included both non-NAbs and NAbs. Cluster V was formed mostly by non-RBDtargeting mAbs that also bound to SARS-CoV. However, these mAbs were not able to neutralize either SARS-CoV-2 or SARS-CoV, suggesting that these mAbs target a conserved non-neutralizing epitope on the S protein. Finally, the two non-RBD mAbs COVA1-03 and COVA1-21 formed single-mAb competition clusters (clusters X and XI, respectively) and showed an unusual competition pattern, because binding of either mAb blocked binding by most of the other mAbs, but not vice versa (figs. S5 and S6 and table S2). We hypothesize that these two mAbs allosterically interfere with mAb binding by causing conformational changes in the S protein that shield or impair most other mAb epitopes. COVA1-21 also efficiently blocked virus infection without blocking ACE2, suggesting an alternative mechanism of neutralization than blocking ACE2 engagement (fig. S4C). The SPR-based clustering was corroborated using biolayer interferometry competition assays on a subset of NAbs (fig. S6). Overall, our data are consistent with the previous identification of multiple antigenic RBD sites for SARS-CoV-2 and additional non-RBD sites on the S protein, as described for SARS-CoV and MERS-CoV (32, 42).

(A) Dendrogram showing hierarchical clustering of the SPR-based cross-competition heat map (table S2). Clusters are numbered I to XI and are depicted with color shading. ELISA binding to SARS-CoV-2 S protein, SARS-CoV S protein, and SARS-CoV-2 RBD as presented by AUC and neutralization IC50 (g/ml) of SARS-CoV-2 is shown in the columns on the left. ELISA AUCs are shown in gray (AUC < 1) or blue (AUC > 1), and neutralization IC50 is shown in gray (>10 g/ml), blue (1 to 10 g/ml), violet (0.1 to 1 g/ml), or purple (0.001 to 0.1 g/ml). Asterisks indicate antibodies that cross-neutralize SARS-CoV pseudovirus. (B) Composite figure demonstrating binding of NTD-mAb COVA1-22 (blue) and RBD mAbs COVA2-07 (green), COVA2-39 (orange), COVA1-12 (yellow), COVA2-15 (salmon), and COVA2-04 (purple) to SARS-CoV-2 spike (gray). The spike model (PDB 6VYB) is fit into the density. (C) Magnification of SARS-CoV-2 spike comparing epitopes of RBD mAbs with the ACE2-binding site (red) and the epitope of mAb CR3022 (blue). (D) Side (left) and top (right) views of the 3D reconstruction of COVA2-15 bound to SARS-CoV-2 S protein. COVA2-15 binds to both the down (magenta) and up (salmon) conformations of the RBD. The RBDs are colored blue in the down conformation and black in the up conformation. The angle of approach for COVA2-15 enables this broader recognition of the RBD while also partially overlapping with the ACE2-binding site and therefore blocking receptor engagement.

To visualize how selected NAbs bound to their respective epitopes, we generated FabSARS-CoV-2 S complexes that were imaged by single-particle negative-stain electron microscopy (EM; Fig. 5, B and C, and fig. S7). We obtained low-resolution reconstruction with six Fabs, including five RBD-binding Fabs from three different competition clusters. COVA1-12 overlapped highly with the epitope of COVA2-39, whereas COVA2-04 approached the RBD at a different angle somewhat similar to that of the cross-binding SARS-CoVspecific mAb CR3022 (42). The EM reconstructions confirmed the RBD as the target of these NAbs but revealed a diversity in approach angles (Fig. 5B). Furthermore, whereas four RBD NAbs interacted with a stoichiometry of one Fab per trimer, consistent with one RBD being exposed in the up state and two in the less accessible down state (13, 43), COVA2-15 bound with a stoichiometry of three per trimer (fig. S7). COVA2-15 was able to bind RBD domains in both the up and down state (Fig. 5D). In either conformation, the COVA2-15 epitope partially overlapped with the ACE2-binding site, and therefore the mAb blocks receptor engagement. The higher stoichiometry of this mAb may explain its unusually strong neutralization potency. None of the epitopes of the five RBD Fabs overlapped with that of CR3022, which is unable to neutralize SARS-CoV-2 (42), although COVA2-04 does approach the RBD from a similar angle as CR3022. The sixth Fab for which we generated a three-dimensional (3D) reconstruction was from the non-RBD mAb COVA1-22 placed in competition cluster IX. EM demonstrated that this mAb bound to the NTD of S1. Such NTD NAbs have also been found for MERS-CoV (44).

Convalescent COVID-19 patients showed strong antiSARS-CoV-2 S proteinspecific B cell responses and developed memory and antibody-producing B cells that may have participated in the control of infection and the establishment of humoral immunity. We isolated 19 NAbs that targeted a diverse range of antigenic sites on the S protein, of which two showed picomolar neutralizing activities (IC50 = 0.007 and 0.009 g/ml or 47 and 60 pM, respectively) against authentic SARS-CoV-2 virus. This illustrates that SARS-CoV-2 infection elicits high-affinity and cross-reactive mAbs targeting the RBD as well as other sites on the S protein. Several of the potent NAbs had VH segments virtually identical to their germline origin, which holds promise for the induction of similar NAbs by vaccination because extensive affinity maturation does not appear to be a requirement for potent neutralization. The most potent NAbs both targeted the RBD on the S protein and fell within the same competition cluster, but were isolated from two different individuals and bore little resemblance genotypically. Although direct comparisons are difficult, the neutralization potency of these and several other mAbs exceeds the potencies of the most advanced HIV-1 and Ebola mAbs under clinical evaluation, as well as the approved anti-RSV mAb palivizumab (45). Through large-scale SPR-based competition assays, we defined NAbs that targeted multiple sites of vulnerability on the RBD and the additional previously undefined non-RBD epitopes on SARS-CoV-2. This is consistent with the identification of multiple antigenic RBD sites for SARS-CoV-2 and the presence of additional non-RBD sites on the S protein of SARS-CoV and MERS-CoV (32). Subsequent structural characterization of these potent NAbs will guide vaccine design, and simultaneous targeting of multiple non-RBD and RBD epitopes with mAb cocktails paves the way for safe and effective COVID-19 prevention and treatment.

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Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability - Science Magazine

Susan Brown, Herman M. Cohn Professor of Agriculture and Life Science and head of Cornells apple breeding program, holds an apple variety used for making rose cider. Credit: Allison Usavage/Cornell University

If you were on Cornells Ithaca campus last fall, you might have found a few cafes with wooden crates full of fruit simply labeled Apple A. The apples have distinctive russet skin dotted with white spots. Take a bite and youll get a complex, nutty sweetness thats not quite like any apple youve ever tasted.

So why does it have such an unremarkable name? Because Apple A isnt ready for the grocery store quite yet. Breeding, licensing and retailing new produce are all complicated processes, and convincing consumers to trade their favorites for something new isnt much easier.

But over the years, the innovative plant breeders at Cornells College of Agriculture and Life Sciences (CALS) have created more than 290 fruit varieties and 165 vegetable varieties. From breeding new varieties that will wow consumers, to marketing those varieties to get them to peoples plates, theyre offering farmers, producers and consumers foods that taste better, have longer growing seasons and are more resistant to threats from diseases, insects and weather.

Susan Brown, Herman M. Cohn Professor of Agriculture and Life Science and head of Cornells apple breeding program, tests the firmness of a new apple variety. Credit: Allison Usavage/Cornell University

When plant breederPhillip Griffithsstarted at CALS in 1999, he says, he and his colleagues focused almost exclusively on breeding plants for disease resistance, higher yields and the other traits growers wanted.

Now the bar is moving even higher, says Griffiths, associate professor in the horticulture section of the School of Integrative Plant Science (SIPS). In recent years, he says, theres been more interest in developing products that are aimed at what consumers want, too.

This shift has opened the door for CALS breeders to show the creative side of their expertise. Right now, the food system is wide open to change, unlike at any point in my lifetime, Griffiths says. Anything can happen.

In 2004, Griffiths decided to grow new varieties of tomatoes that would offer consumers more diverse color and flavor choices. I was originally interested in coming up with a finger-shaped tomato that could be a substitute for baby carrots, he says. But the new fruit didnt grow quite the way he was hoping.

When researchers cross-breed plants to enhance or minimize certain traits, its a genetic gamble to land the winning combination of characteristics. A plant with one desirable quality, like taste, crossed with a plant that has another ideal trait, like texture, might produce offspring that has one, both or neither of those qualities. And traits can skip generations and reappear months or years later.

Phillip Griffiths, associate professor of horticulture, has been developing chili pepper tomatoes that come in seven different colors. His other edible inventions include a Galaxy Suite of heirloom tomatoes and new varieties of cabbage, kale and radishes. Credit: Isabel Branstrom/Cornell University

By combining different shapes, I eventually developed tomatoes that looked exactly like chili peppers, Griffiths said. But he wasnt discouraged by the odd shape. He was inspired. Since tomatoes and chili peppers are two of the most popular foods in the world, I thought it might have a lot of appeal.

This variety still needs a few more years to ensure that offspring remain stable from generation to generation, so that farmers and consumers receive a predictable product. From idea to market, this variety will amount to some 15 years of breeding work.

Marketing a new creation also presents a substantial challenge.

One of the biggest obstacles for breeders is that consumers and the food production pipeline dont recognize specialty crops as unique products.

I could rattle off 50 different cultivars of butternut squash, but most are sold under the commodity name of butternut squash, saysMichael Mazourek, Ph.D. 08, associate professor in the plant breeding and genetics section of SIPS. You can come up with a better variety, but if people dont recognize it, you can be stuck clawing for traction and impact in the market.

Different breeding lines of butternut squash are cut open before testing their performance in the oven. Credit: Row 7 Seed Company/Cornell University

Part of the problem is that most breeders efforts tend to be invisibly absorbed into the commercial food chain. Researchers might give their budding varieties unique names, says Mary Kreitinger, executive director of theVegetable Breeding Institutein the plant breeding and genetics section of SIPS. But unless a seed company markets our variety by name, we usually have no way to track it and dont know how or where it gets to consumers.

Mazourek broke through the anonymity barrier by partnering with Manhattan chef Dan Barber and grower Matthew Goldfarb to co-foundRow 7 Seed Company. Their goal is to bring diverse produce to farms and consumers by working with chefs who embrace new ingredients.

I did it to fill a void in the market, says Mazourek, who gets no money from or equity in the company. I like to create things that stand out, and we use enjoyment of flavor to drive change.

Now Honeynut squash a smaller, more flavorful variety of butternut squash that Mazourek helped develop has earned name recognition on the national market.

Credit: Clive Howard/Cornell University

Establishing a new variety in the marketplace is still an uphill battle, and not always in a breeders best interests, says Jessica Lyga, senior licensing and business development officer at Cornells Center for Technology Licensing. We do market research, she says, to see if the new variety would be just another entry among 200 in a commodity market or a shining star thats clearly better than whats out there.

Credit: Clive Howard/Cornell University

Consumers are willing to try a new type of apple once, saysSusan Brown, the Herman M. Cohn Professor of Agriculture and Life Science and head of Cornells apple breeding program. But repeat sales determine if a new apple can make a dent in an already competitive market.

For SnapDragon, one of Browns best-known apple varieties, the decision to go big was easy. The first time I bit into it, I said, Oh my gosh, and everyone who tried it agreed, she says. Ive never been so confident in a fruit.

The apple was released in 2015, following the 2014 release of another variety, RubyFrost. Crunch Time Apple Growers, a cooperative open to all growers in New York state, formed a partnership with Cornell and licensed the rights to grow and sell both of Browns varieties. Crunch Times marketing team then leveraged social media to generate interest among its audiences.

In 2018, Crunch Time doubled the volume of SnapDragon sold over the previous year. Its on track to double again. RubyFrost is also recording strong, steady growth. SnapDragon has been a hit on the international market, as well, including in Canada, Israel and Vietnam.

CALS breeders aim to help New York state farmers thrive, by making crops more sustainable and produce more diverse, says Mazourek, and CALS researchers work closely with farmers on every aspect of crop selection and growing. As academics, we want to help understand the world more clearly, Mazourek says. But in the end, we want our work to translate into better lives.

Still, the occasional consumer hit is welcome.

Perhaps the next one is sitting in a wooden crate labeled Apple A.

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From Seed to Supermarket: What Does It Really Take to Put Produce on Your Plate? - SciTechDaily