Government Executive - Authors - Dr. Francis Collins

Most Vaccine-Hesitant People Remain Willing to Change Their Minds

Dr. Francis Collins — Tue, 05 Oct 2021 11:32:59 -0400

As long and difficult as this pandemic has been, I remain overwhelmingly grateful for the remarkable progress being made, including the hard work of so many people to develop rapidly and then deploy multiple life-saving vaccines. And yet, grave concerns remain that vaccine hesitancy—the reluctance of certain individuals and groups to get themselves and their children vaccinated—could cause this pandemic to go on much longer than it should.

We’re seeing the results of such hesitancy in the news every day, highlighting the rampant spread of COVID-19 that’s stretching our healthcare systems and resources dangerously thin in many places. The vast majority of those currently hospitalized with COVID-19 are unvaccinated, and most of those tragic 2,000 deaths each day could have been prevented. The stories of children and adults who realized too late the importance of getting vaccinated are heartbreaking.

With these troubling realities in mind, I was encouraged to see a new study in the journal JAMA Network Open that tracked vaccine hesitancy over time in a random sample of more than 4,600 Americans. This national study shows that vaccine hesitancy isn’t set in stone. Over the course of this pandemic, hesitancy has decreased, and many who initially said no are now getting their shots. Many others who remain unvaccinated lean toward making an appointment.

The findings come from Aaron Siegler and colleagues, Emory University, Atlanta. They were interested in studying how entrenched vaccine hesitancy would be over time. The researchers also wanted to see how often those who were initially hesitant went on to get their shots.

To find out, they recruited a diverse, random, national sampling of individuals from August to December 2020, just before the first vaccines were granted Emergency Use Approval and became widely available. They wanted to get a baseline, or starting characterization, on vaccine hesitancy. Participants were asked two straightforward questions, “Have you received the COVID-19 vaccine?” and “How likely are you to get it in the future?” From March to April 2021, the researchers followed up by asking participants the same questions again when vaccines were more readily available to many (although still not all) adults.

The survey’s initial results showed that nearly 70 percent of respondents were willing to get vaccinated at the outset, with the other 30 percent expressing some hesitancy. The good news is among the nearly 3,500 individuals who answered the survey at follow-up, about a third who were initially vaccine hesitant already had received at least one shot. Another third also said that they’d now be willing to get the vaccine, even though they hadn’t just yet.

Among those who initially expressed a willingness to get vaccinated, about half had done so at follow up by spring 2021 (again, some still may not have been eligible). Forty percent said they were likely to get vaccinated. However, 7 percent of those who were initially willing said they were now less likely to get vaccinated than before.

There were some notable demographic differences. Folks over age 65, people who identified as non-Hispanic Asians, and those with graduate degrees were most likely to have changed their minds and rolled up their sleeves. Only about 15 percent in any one of these groups said they weren’t willing to be vaccinated. Most reluctant older people ultimately got their shots.

The picture was more static for people aged 45 to 54 and for those with a high school education or less. The majority of those remained unvaccinated, and about 40 percent still said they were unlikely to change their minds.

At the outset, people of Hispanic heritage were as willing as non-Hispanic whites to get vaccinated. At follow-up, however, fewer Hispanics than non-Hispanic whites said they’d gotten their shots. This finding suggests that, in addition to some hesitancy, there may be significant barriers still to overcome to make vaccination easier and more accessible to certain groups, including Hispanic communities from Central and South America.

Willingness among non-Hispanic Blacks was consistently lowest, but nearly half had gotten at least one dose of vaccine by the time they completed the second survey. That’s comparable to the vaccination rate in white study participants. For more recent data on vaccination rates by race/ethnicity, see this report from the Kaiser Family Foundation.

Overall, while a small number of respondents grew more reluctant over time, most people grew more comfortable with the vaccines and were more likely to say they’d get vaccinated, if they hadn’t already. In fact, by the end of the study, the hesitant group had shrunk from 31 to 15 percent. It’s worth noting that the researchers checked the validity of self-reported vaccination using antibody tests and the results matched up rather well.

This is all mostly good news, but there’s clearly more work to do. An estimated 70 million eligible Americans have yet to get their first shot, and remain highly vulnerable to infection and serious illness from the Delta variant. They are capable of spreading the virus to other vulnerable people around them (including children), and incubating the next variants that might provide more resistance to the vaccines and therapies. They are also at risk for Long COVID, even after a relatively mild acute illness.

The work ahead involves answering questions and addressing concerns from people who remain hesitant. It’s also incredibly important to reach out to those willing, but unvaccinated, individuals, to see what can be done to help them get their shots. If you happen to be one of those, it’s easy to find the places near you that have free vaccines ready to administer. Go to vaccines.gov, or punch 438829 on your cell phone and enter your zip code—in less than a minute you will get the location of vaccine sites nearby.

Nearly 400 million COVID-19 vaccine doses have been administered in communities all across the United States. More than 600,000 more are being administered on average each day. And yet, more than 80,000 new infections are still reported daily, and COVID-19 still steals the lives of about 2,000 mostly unvaccinated people each day.

These vaccines are key for protecting yourself and ultimately beating this pandemic. As these findings show, the vast majority of Americans understand this and either have been vaccinated or are willing to do so. Let’s keep up the good work, and see to it that even more minds will be changed—and more individuals protected before they may find it’s too late.

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Infections with ‘U.K. Variant’ B.1.1.7 Have Greater Risk of Mortality

Dr. Francis Collins — Tue, 30 Mar 2021 12:20:02 -0400

Since the genome sequence of SARS-CoV-2, the virus responsible for COVID-19, was first reported in January 2020, thousands of variants have been reported. In the vast majority of cases, these variants, which arise from random genomic changes as SARS-CoV-2 makes copies of itself in an infected person, haven’t raised any alarm among public health officials. But that’s now changed with the emergence of at least three variants carrying mutations that potentially make them even more dangerous.

At the top of this short list is a variant known as B.1.1.7, first detected in the United Kingdom in September 2020. This variant is considerably more contagious than the original virus. It has spread rapidly around the globe and likely accounts already for at least one-third of all cases in the United States. Now comes more troubling news: emerging evidence indicates that infection with this B.1.1.7 variant also comes with an increased risk of severe illness and death.

The findings, reported in Nature, come from Nicholas Davies, Karla Diaz-Ordaz, and Ruth Keogh, London School of Hygiene and Tropical Medicine. The London team earlier showed that this new variant is 43 to 90 percent more transmissible than pre-existing variants that had been circulating in England. But in the latest paper, the researchers followed up on conflicting reports about the virulence of B.1.1.7.

They did so with a large British dataset linking more than 2.2 million positive SARS-CoV-2 tests to 17,452 COVID-19 deaths from September 1, 2020, to February 14, 2021. In about half of the cases (accounting for nearly 5,000 deaths), it was possible to discern whether or not the infection had been caused by the B.1.1.7 variant.

Based on this evidence, the researchers calculated the risk of death associated with B.1.1.7 infection. Their estimates suggest that B.1.1.7 infection was associated with 55 percent greater mortality compared to other SARS-CoV-2 variants over this time period.

For a 55- to 69-year-old male, this translates to a 0.9-percent absolute, or personal, risk of death, up from 0.6 percent for the older variants. That means nine in every 1,000 people in this age group who test positive with the B.1.1.7 variant would be expected to die from COVID-19 a month later. For those infected with the original virus, that number would be six.

These findings are in keeping with those of another recent study reported in the British Medical Journal. In that case, researchers at the University of Exeter and the University of Bristol found that the B.1.1.7 variant was associated with a 64 percent greater chance of dying compared to earlier variants. That’s based on an analysis of data from more than 100,000 COVID-19 patients in the U.K. from October 1, 2020, to January 28, 2021.

That this variant comes with increased disease severity and mortality is particularly troubling news, given the highly contagious nature of B.1.1.7. In fact, Davies’ team has concluded that the emergence of new SARS-CoV-2 variants now threaten to slow or even cancel out improvements in COVID-19 treatment that have been made over the last year. These variants include not only B1.1.7, but also B.1.351 originating in South Africa and P.1 from Brazil.

The findings are yet another reminder that, while we’re making truly remarkable progress in the fight against COVID-19 with increasing availability of safe and effective vaccines (more than 45 million Americans are now fully immunized), now is not the time to get complacent. This devastating pandemic isn’t over yet.

The best way to continue the fight against all SARS-CoV-2 variants is for each one of us to do absolutely everything we can to stop their spread. This means that taking the opportunity to get vaccinated as soon as it is offered to you, and continuing to practice those public health measures we summarize as the three Ws: Wear a mask, Watch your distance, Wash your hands often.

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Study of Healthcare Workers Shows COVID-19 Immunity Lasts Many Months

Dr. Francis Collins — Wed, 09 Dec 2020 10:38:20 -0500

Throughout the COVID-19 pandemic, healthcare workers around the world have shown willingness to put their own lives on the line for their patients and communities. Unfortunately, many have also contracted SARS-CoV-2, the coronavirus that causes of COVID-19, while caring for patients. That makes these frontline heroes helpful in another way in the fight against SARS-CoV-2: determining whether people who have recovered from COVID-19 can be reinfected by the virus.

New findings from a study of thousands of healthcare workers in England show that those who got COVID-19 and produced antibodies against the virus are highly unlikely to become infected again, at least over the several months that the study was conducted. In the rare instances in which someone with acquired immunity for SARS-CoV-2 subsequently tested positive for the virus within a six month period, they never showed any signs of being ill.

Some earlier studies have shown that people who survive a COVID-19 infection continue to produce protective antibodies against key parts of the virus for several months. But how long those antibodies last and whether they are enough to protect against reinfection have remained open questions.

In search of answers, researchers led by David Eyre, University of Oxford, England, looked to more than 12,000 healthcare workers at Oxford University Hospitals from April to November 2020. At the start of the study, 11,052 of them tested negative for antibodies against SARS-CoV-2, suggesting they hadn’t had COVID-19. But the other 1,246 tested positive for antibodies, evidence that they’d already been infected.

After this initial testing, all participants received antibody tests once every two months and diagnostic tests for an active COVID-19 infection at least every other week. What the researchers discovered was rather interesting. Eighty-nine of the 11,052 healthcare workers who tested negative at the outset later got a symptomatic COVID-19 infection. Another 76 individuals who originally tested negative for antibodies tested positive for COVID-19, despite having no symptoms.

Here’s the good news: Just three of these more than 1400 antibody-positive individuals subsequently tested positive for SARS-CoV-2. What’s more, not one of them had any symptoms of COVID-19.

The findings, which were posted as a pre-print on medRxiv, suggest that acquired immunity from an initial COVID-19 infection offers protection against reinfection for six months or maybe longer. Questions remain about whether the acquired immunity is due to the observed antibodies alone or their interplay with other immune cells. It will be important to continue to follow these healthcare workers even longer, to learn just how long their immune protection might last.

Meanwhile, more than 15 million people in the United States have now tested positive for COVID-19, leading to more than 285,000 deaths. Last week, the U.S. reported for the first time more than 200,000 new infections, with hospitalizations and deaths also on the rise.

While the new findings on reinfection come as good news to be sure, it’s important to remember that the vast majority of the 328 million Americans still remain susceptible to this life-threatening virus. So, throughout this holiday season and beyond—as we eagerly await the approval and widespread distribution of vaccines—we must all continue to do absolutely everything we can to protect ourselves, our loved ones, and our communities from COVID-19.

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Face Coverings Could Save 130,000 American Lives from COVID-19 by March

Dr. Francis Collins — Wed, 04 Nov 2020 08:08:11 -0500

The COVID-19 pandemic has already claimed the lives of more than 230,000 Americans, the population of a mid-sized U.S. city. As we look ahead to winter and the coming flu season, the question weighing on the minds of most folks is: Can we pull together to contain the spread of this virus and limit its growing death toll?

I believe that we can, but only if each of us gets fully engaged with the public health recommendations. We need all Americans to do the right thing and wear a mask in public to protect themselves and their communities from spreading the virus. Driving home this point is a powerful new study that models just how critical this simple, low-cost step will be this winter and through the course of this pandemic.

Right now, it’s estimated that about half of Americans always wear a mask in public. According to the new study, published in Nature Medicine, if this incomplete rate of mask-wearing continues and social distancing guidelines are not adhered to, the total number of COVID-19 deaths in the United States could soar to more than 1 million by the end of February.

However, the model doesn’t accept that we’ll actually end up at this daunting number. It anticipates that once COVID mortality reaches a daily threshold of 8 deaths per 1 million citizens, U.S. states would reinstate limits on social and economic activity—as much of Europe is now doing. If so, the model predicts that by March, such state-sanctioned measures would cut the projected number of deaths in half to about 510,000—though that would still add another 280,000 lives lost to this devastating virus.

The authors, led by Christopher Murray, Institute of Health Metrics and Evaluations, University of Washington School of Medicine, Seattle, show that we can do better than that. But doing better will require action by all of us. If 95 percent of people in the U.S. began wearing masks in public right now, the death toll would drop by March from the projected 510,000 to about 380,000.

In other words, if most Americans pulled together to do the right thing and wore a mask in public, this simple, selfless act would save more than 130,000 lives in the next few months alone. If mask-wearers increased to just 85 percent, the model predicts it would save about 96,000 lives across the country.

What’s important here aren’t the precise numbers. It’s the realization that, under any scenario, this pandemic is far from over, and, together, we have it within our power to shape what happens next. If more people make the decision to wear masks in public today, it could help to delay—or possibly even prevent—the need for future shutdowns. As such, the widespread use of face coverings has the potential to protect lives while also minimizing further damage to the economy and American livelihoods. It’s a point that NIH’s Anthony Fauci and colleagues presented quite well in a recent commentary in JAMA.

As we anxiously await the approved vaccines for COVID-19 and other advances in its prevention and treatment, the life-saving potential of face coverings simply can’t be overstated. I know that many people are tired of this message, and, unfortunately, mask-wearing has been tangled up in political perspectives at this time of deep divisions in our country.

But think about it in the same way you think about putting on your seat belt—a minor inconvenience that can save lives. I’m careful to wear a mask outside my home every time I’m out and about. But, ultimately, saving lives and livelihoods as we head into these winter months will require a collective effort from all of us.

To do so, each of us needs to follow these three W’s: Wear a mask. Watch your distance (stay 6 feet apart). Wash your hands often.

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Researchers Publish Encouraging Early Data on COVID-19 Vaccine

Dr. Francis Collins — Thu, 16 Jul 2020 10:07:19 -0400

People all around the globe are anxiously awaiting development of a safe, effective vaccine to protect against the deadly threat of coronavirus disease 2019 (COVID-19). Evidence is growing that biomedical research is on track to provide such help, and to do so in record time.

Just two days ago, in a paper in the New England Journal of Medicine, researchers presented encouraging results from the vaccine that’s furthest along in U.S. human testing: an innovative approach from NIH’s Vaccine Research Center (VRC), in partnership with Moderna Inc., Cambridge, MA. The centerpiece of this vaccine is a small, non-infectious snippet of messenger RNA (mRNA). Injecting this mRNA into muscle will spur a person’s own body to make a key viral protein, which, in turn, will encourage the production of protective antibodies against SARS-CoV-2—the novel coronavirus that causes COVID-19.

While it generally takes five to 10 years to develop a vaccine against a new infectious agent, we simply don’t have that time with a pandemic as devastating as COVID-19. Upon learning of the COVID-19 outbreak in China early this year, and seeing the genome sequence of SARS-CoV-2 appear on the internet, researchers with NIH’s National Institute of Allergy and Infectious Diseases (NIAID) carefully studied the viral instructions, focusing on the portion that codes for a spike protein that the virus uses to bind to and infect human cells.

Because of their experience with the original SARS virus back in the 2000s, they thought a similar approach to vaccine development would work and modified an existing design to reflect the different sequence of the SARS-CoV-2 spike protein. Literally within days, they had created a vaccine in the lab. They then went on to work with Moderna, a biotech firm that’s produced personalized cancer vaccines. All told, it took just 66 days from the time the genome sequence was made available in January to the start of the first-in-human study described in the new peer-reviewed paper.

In the NIH-supported phase 1 human clinical trial, researchers found the vaccine, called mRNA-1273, to be safe and generally well tolerated. Importantly, human volunteers also developed significant quantities of neutralizing antibodies that target the virus in the right place to block it from infecting their cells.

Conducted at Kaiser Permanente Washington Health Research Institute, Seattle; and Emory University School of Medicine, Atlanta, the trial led by Kaiser Permanente’s Lisa Jackson involved healthy adult volunteers. Each volunteer received two vaccinations in the upper arm at one of three doses, given approximately one month apart.

The volunteers will be tracked for a full year, allowing researchers to monitor their health and antibody production. However, the recently published paper provides interim data on the phase 1 trial’s first 45 participants, ages 18 to 55, for the first 57 days after their second vaccination. The data revealed:

No volunteers suffered serious adverse events.
Optimal dose to elicit high levels of neutralizing antibody activity, while also protecting patient safety, appears to be 100 micrograms. Doses administered in the phase 1 trial were either 25, 100, or 250 micrograms.
More than half of the volunteers reported fatigue, headache, chills, muscle aches, or pain at the injection site. Those symptoms were most common after the second vaccination and in volunteers who received the highest vaccine dose. That dose will not be used in larger trials.
Two doses of 100 micrograms of the vaccine prompted a robust immune response, which was last measured 43 days after the second dose. These responses were actually above the average levels seen in blood samples from people who had recovered from COVID-19.

These encouraging results are being used to inform the next rounds of human testing of the mRNA-1273 vaccine. A phase 2 clinical trial is already well on its way to recruiting 600 healthy adults.This study will continue to profile the vaccine’s safety, as well as its ability to trigger an immune response.

Meanwhile, later this month, a phase 3 clinical trial will begin enrolling 30,000 volunteers, with particular focus on recruitment in regions and populations that have been particularly hard hit by the virus.

The design of that trial, referred to as a “master protocol,” had major contributions from the Accelerating COVID-19 Therapeutic Interventions and Vaccine (ACTIV) initiative, a remarkable public-private partnership involving 20 biopharmaceutical companies, academic experts, and multiple federal agencies. Now, a coordinated effort across the U.S. government, called Operation Warp Speed, is supporting rapid conduct of these clinical trials and making sure that millions of doses of any successful vaccine will be ready if the vaccine proves save and effective.

Results of this first phase 3 trial are expected in a few months. If you are interested in volunteering for these or other prevention trials, please check out NIH’s new COVID-19 clinical trials network.

There’s still a lot of work that remains to be done, and anything can happen en route to the finish line. But by pulling together, and leaning on the very best science, I am confident that we will be able rise to the challenge of ending this pandemic that has devastated so many lives.

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Meet the Researcher Leading NIH’s COVID-19 Vaccine Development Efforts

Dr. Francis Collins — Thu, 09 Jul 2020 13:28:00 -0400

A safe, effective vaccine is the ultimate tool needed to end the coronavirus disease 2019 (COVID-19) pandemic. Biomedical researchers are making progress every day towards such a vaccine, whether it’s devising innovative technologies or figuring out ways to speed human testing. In fact, just this week, NIH’s National Institute of Allergy and Infectious Diseases (NIAID) established a new clinical trials network that will enroll tens of thousands of volunteers in large-scale clinical trials testing a variety of investigational COVID-19 vaccines.

Among the vaccines moving rapidly through the development pipeline is one developed by NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC), in partnership with Moderna, Inc., Cambridge, MA. So, I couldn’t think of a better person to give us a quick overview of the COVID-19 vaccine research landscape than NIH’s Dr. John Mascola, who is Director of the VRC. Our recent conversation took place via videoconference, with John linking in from his home in Rockville, MD, and me from my place in nearby Chevy Chase. Here’s a condensed transcript of our chat:

Collins: Vaccines have been around since Edward Jenner and smallpox in the late 1700s. But how does a vaccine actually work to protect someone from infection?

Mascola: The immune system works by seeing something that’s foreign and then responding to it. Vaccines depend on the fact that if the immune system has seen a foreign protein or entity once, the second time the immune response will be much brisker. So, with these principles in mind, we vaccinate using part of a viral protein that the immune system will recognize as foreign. The response to this viral protein, or antigen, calls in specialized T and B cells, the so-called memory cells, and they remember the encounter. When you get exposed to the real thing, the immune system is already prepared. Its response is so rapid that you clear the virus before you get sick.

Collins: What are the steps involved in developing a vaccine?

Mascola: One can’t make a vaccine, generally speaking, without knowing something about the virus. We need to understand its surface proteins. We need to understand how the immune system sees the virus. Once that knowledge exists, we can make a candidate vaccine in the laboratory pretty quickly. We then transfer the vaccine to a manufacturing facility, called a pilot plant, that makes clinical grade material for testing. When enough testable material is available, we do a first-in-human study, often at our vaccine clinic at the NIH Clinical Center.

If those tests look promising, the next big step is finding a pharmaceutical partner to make the vaccine at large scale, seek regulatory approval, and distribute it commercially. That usually takes a while. So, from start to finish, the process often takes five or more years.

Collins: With this global crisis, we obviously don’t have five years to wait. Tell us about what the VRC started to do as soon as you learned about the outbreak in Wuhan, China.

Mascola: Sure. It’s a fascinating story. We had been talking with NIAID Director Dr. Anthony Fauci and our colleagues about how to prepare for the next pandemic. Pretty high on our list were coronaviruses, having already worked on past outbreaks of SARS and MERS [other respiratory diseases caused by coronaviruses]. So, we studied coronaviruses and focused on the unique spike protein crowning their surfaces. We designed a vaccine that presented the spike protein to the immune system.

Collins: Knowing that the spike protein was likely your antigen, what was your approach to designing the vaccine?

Mascola: Our approach was a nucleic acid-based vaccine. I’m referring to vaccines that are based on genetic material, either DNA or RNA. It’s this type of vaccine that can be moved most rapidly into the clinic for initial testing.

When we learned of the outbreak in Wuhan, we simply accessed the nucleic acid sequence of SARS-CoV-2, the novel coronavirus that causes COVID-19. Most of the sequence was on a server from Chinese investigators. We looked at the spike sequence and built that into an RNA vaccine. This is called in silico vaccine design. Because of our experience with the original SARS back in the 2000s, we knew its sequence and we knew this approach worked. We simply modified the vaccine design to the sequence of the spike protein of SARS-CoV-2. Literally within days, we started making the vaccine in the lab.

At the same time, we worked with a biotechnology company called Moderna that creates personalized cancer vaccines. From the time the sequence was made available in early January to the start of the first in-human study, it was about 65 days.

Collins: Wow! Has there ever been a vaccine developed in 65 days?

Mascola: I don’t think so. There are a lot of firsts with COVID, and vaccine development is one of them.

Collins: For the volunteers who enrolled in the phase 1 study, what was actually in the syringe?

Mascola: The syringe included messenger RNA (mRNA), the encoded instructions for making a specific protein, in this case the spike protein. The mRNA is formulated in a lipid nanoparticle shell. The reason is mRNA is less stable than DNA, and it doesn’t like to hang around in a test tube where enzymes can break it down. But if one formulates it just right into a nanoparticle, the mRNA is protected. Furthermore, that protective particle allows one to inject it into muscle and facilitates the uptake of the mRNA into the muscle cells. The cells translate the mRNA into spike proteins, and the immune system sees them and mounts a response.

Collins: Do muscle cells know how to take that protein and put it on their cell surfaces, where the immune system can see it?

Mascola: They do if the mRNA is engineered just the right way. We’ve been doing this with DNA for a long time. With mRNA, the advantage is that it just has to get into the cell [not into the nucleus of the cell as it does for DNA]. But it took about a decade of work to figure out how to do nucleotide silencing, which allows the cell to see the mRNA, not destroy it, and actually treat it as a normal piece of mRNA to translate into protein. Once that was figured out, it becomes pretty easy to make any specific vaccine.

Collins: That’s really an amazing part of the science. While it seems like this all happened in a blink of an eye, 65 days, it was built on years of basic science work to understand how cells treat mRNA. What’s the status of the vaccine right now?

Mascola: Early data from the phase 1 study are very encouraging. There’s a manuscript in preparation that should be out shortly showing that the vaccine was safe. It induced a very robust immune response to that spike protein. In particular, we looked for neutralizing antibodies, which are the ones that attach to the spike, blocking the virus from binding to a cell. There’s a general principle in vaccine development: if the immune system generates neutralizing antibodies, that’s a very good sign.

Collins: You’d be the first to say that you’re not done yet. Even though those are good signs, that doesn’t prove that this vaccine will work. What else do you need to know?

Mascola: The only real way to learn if a vaccine works is to test it in people. We break clinical studies into phases 1, 2, and 3. Phase 1 has already been done to evaluate safety. Phase 2 is a larger evaluation of safety and immune response. That’s ongoing and has enrolled 500 or 600 people, which is good. The plan for the phase 3 study will be to start in July. Again, that’s incredibly fast, considering that we didn’t even know this virus existed until January.

Collins: How many people do you need to study in a phase 3 trial?

Mascola: We’re thinking 20,000 or 30,000.

Collins: And half get the vaccine and half get a placebo?

Mascola: Sometimes it can be done differently, but the classic approach is half placebo, half vaccine.

Collins: We’ve been talking about the VRC-Moderna nucleic acid vaccine. But there are others that are coming along pretty quickly. What other strategies are being employed, and what are their timetables?

Mascola: There are many dozens of vaccines under development. The response has been extraordinary by academic groups, biotech companies, pharmaceutical companies, and NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership. I don’t think I’ve ever seen so much activity in a vaccine space moving ahead at such a rapid clip.

As far as being ready for advanced clinical trials, there are a just handful and they involve different types of vaccines. At least three nucleic acid vaccines are in clinical trials. There are also two vaccines that use proteins, which is a more classic approach.

In addition, there are several vaccines based on a viral vector. To make these, one puts the genes for the spike protein inside an adenovirus, which is an innocuous cold virus, and injects it into muscle. In regard to phase 3 trials, there are maybe three or four vaccines that could be formally in such tests by the fall.

Collins: How is it possible to do this so much more rapidly than in the past, without imposing risks?

Mascola: It’s a really important question, Francis. A number of things are being done in parallel, and that wouldn’t usually be the case. We can get a vaccine into a first-in-human study much more quickly because of time-saving technologies.

But the real important point is that for the phase 3 trial, there are no timesavers. One must enroll 30,000 people and watch them over months in a very rigorous, placebo-controlled environment. The NIH has stood up what’s called a Data Safety Monitoring Board for all the trials. That’s an independent group of investigators that will review all vaccine trial data periodically. They can see what the data are showing: Should the trial be stopped early because the vaccine is working? Is there a safety signal that raises concern?

While the phase 3 trial is going on, the U.S. government also will be funding large-scale manufacture of the vaccine. Traditionally, you would do the vaccine trial, wait until it’s all done, and analyze the data. If it worked, you’d build a vaccine plant to make enough material, which takes two or three years, and then go to the Food and Drug Administration (FDA) for regulatory approval.

Everything here is being done in parallel. So, if the vaccine works, it’s already in supply. And we have been engaging the FDA to get real-time feedback. That does save a lot of time.

Collins: Is it possible that we’ll manufacture a whole lot of doses that may have to be thrown out if the vaccine doesn’t work?

Mascola: It certainly is possible. One would like to think that for coronaviruses, vaccines are likely to work, in part because the natural immune response clears them. People get quite sick, but eventually the immune system clears the virus. So, if we can prime it with a vaccine, there is reason to believe vaccines should work.

Collins: If the vaccine does work, will this be for lifelong prevention of COVID-19? Or will this be like the flu, where the virus keeps changing and new versions of the vaccine are needed every year?

Mascola: From what we know about coronaviruses, we think it’s likely COVID-19 is not like the flu. Coronaviruses do have some mutation rate, but the data suggest it’s not as rapid as influenza. If we’re fortunate, the vaccine won’t need to be changed. Still, there’s the matter of whether the immunity lasts for a year, five years, or 10 years. That we don’t know without more data.

Collins: Do we know for sure that somebody who has had COVID-19 can’t get it again a few months later?

Mascola: We don’t know yet. To get the answer, we must do natural history studies, where we follow people who’ve been infected and see if their risk of getting the infection is much lower. Although classically in virology, if your immune system shows neutralizing antibodies to a virus, it’s very likely you have some level of immunity.

What’s a bit tricky is there are people who get very mild symptoms of COVID-19. Does that mean their immune system only saw a little bit of the viral antigen and didn’t respond very robustly? We’re not sure that everyone who gets an infection is equally protected. That’s going to require a natural history study, which will take about a year of follow-up to get the answers.

Collins: Let’s go back to trials that need to happen this summer. You talked about 20,000 to 30,000 people needing to volunteer just for one vaccine. Whom do you want to volunteer?

Mascola: The idea with a phase 3 trial is to have a broad spectrum of participation. To conduct a trial of 30,000 people is an enormous logistical operation, but it has been done for the rotavirus and HPV vaccines. When you get to phase 3, you don’t want to enroll just healthy adults. You want to enroll people who are representative of the diverse population that you want to protect.

Collins: Do you want to enrich for high-risk populations? They’re the ones for whom we hope the vaccine will provide greatest benefit: for example, older people with chronic illnesses, African Americans, and Hispanics.

Mascola: Absolutely. We want to make sure that we can feel comfortable to recommend the vaccine to at-risk populations.

Collins: Some people have floated another possibility. They ask why do we need expensive, long-term clinical trials with tens of thousands of people? Couldn’t we do a human challenge trial in which we give the vaccine to some healthy, young volunteers, wait a couple of weeks, and then intentionally expose them to SARS-CoV-2. If they don’t get sick, we’re done. Are challenge studies a good idea for COVID-19?

Mascola: Not right now. First, one has to make a challenge stock of the SARS-CoV-2 that’s not too pathogenic. We don’t want to make something in the lab that causes people to get severe pneumonia. Also, for challenge studies, it would be preferable to have a very effective small drug or antibody treatment on hand. If someone were to get sick, you could take care of the infection pretty readily with the treatments. We don’t have curative treatments, so the current thinking is we’re not there yet for COVID-19 challenge studies [1]. If you look at our accelerated timeline, formal vaccine trials still may be the fastest and safest way to get the answers.

Collins: I’m glad you’re doing it the other way, John. It’s going to take a lot of effort. You’re going to have to go somewhere where there is still ongoing spread, otherwise you won’t know if the vaccine works or not. That’s going to be tricky.

Mascola: Yes. How do we know where to test the vaccine? We are using predictive analytics, which is just a fancy way of saying that we are trying to predict where in the country there will be ongoing transmission. If we can get really good at it, we’ll have real-time data to say transmission is ongoing in a certain area. We can vaccinate in that community, while also possibly protecting people most at risk.

Collins: John, this conversation has been really informative. What’s your most optimistic view about when we might have a COVID-19 vaccine that’s safe and effective enough to distribute to the public?

Mascola: An optimistic scenario would be that we get an answer in the phase 3 trial towards the end of this year. We have scaled up the production in parallel, so the vaccine should be available in great supply. We still must allow for the FDA to review the data and be comfortable with licensing the vaccine. Then we must factor in a little time for distributing and recommending that people get the vaccine.

Collins: Well, it’s wonderful to have someone with your skills, experience, and vision taking such a leading role, along with your many colleagues at the Vaccine Research Center. People like Kizzmekia Corbett, Barney Graham, and all the others who are a part of this amazing team that you’ve put together, overseen by Dr. Fauci.

While there is still a ways to go, we can take pride in how far we have come since this virus emerged just about six months ago. In my 27 years at NIH, I’ve never seen anything quite like this. There’s been a willingness among people to set aside all kinds of other concerns. They’ve gathered around the same table, worked on vaccine design and implementation, and gotten out there in the real world to launch clinical trials.

John, thank you for what you are doing 24/7 to make this kind of progress possible. We’re all watching, hoping, and praying that this will turn out to be the answer that people desperately need after such a terribly difficult time so far in 2020. I believe 2021 will be a very different kind of experience, largely because of the vaccine science that we’ve been talking about today.

Mascola: Thank you so much, Francis. And thanks for recognizing all the people behind the scenes who are making this happen. They’re working really hard!

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The Critical Need for Reliable Antibody Testing for COVID-19

Dr. Francis Collins — Thu, 04 Jun 2020 11:49:07 -0400

There’s been a great deal of discussion about whether people who recover from coronavirus disease 2019 (COVID-19), have neutralizing antibodies in their bloodstream to guard against another infection. Lots of interesting data continue to emerge, including a recent preprint from researchers at Sherman Abrams Laboratory in Brooklyn, N.Y. They tested 11,092 people for antibodies in May at a local urgent care facility and found nearly half had long-lasting IgG antibodies, a sign of exposure to the novel coronavirus SARS-CoV-2, the cause of COVID-19. The researchers also found a direct correlation between the severity of a person’s symptoms and their levels of IgG antibodies.

This study and others remind us of just how essential antibody tests will be going forward to learn more about this challenging pandemic. These assays must have high sensitivity and specificity, meaning there would be few false negatives and false positives, to tell us more about a person’s exposure to SARS-CoV-2. While there are some good tests out there, not all are equally reliable.

Recently, I had a chance to discuss COVID-19 antibody tests, also called serology tests, with Dr. Norman “Ned” Sharpless, Director of NIH’s National Cancer Institute (NCI). Among his many talents, Dr. Sharpless is an expert on antibody testing for COVID-19. You might wonder how NCI got involved in COVID-19 testing. Well, you’re going to find out. Our conversation took place while videoconferencing, with him connecting from North Carolina and me linking in from my home in Maryland. Here’s a condensed transcript of our chat:

Collins: Ned, thanks for joining me. Maybe we should start with the basics. What are antibodies anyway?

Sharpless: Antibodies are proteins that your body makes as part of the learned immune system. It’s the immunity that responds to a bacterium or a virus. In general, if you draw someone’s blood after an infection and test it for the presence of these antibodies, you can often know whether they’ve been infected. Antibodies can hang around for quite a while. How long exactly is a topic of great interest, especially in terms of the COVID-19 pandemic. But we think most people infected with coronavirus will make antibodies at a reasonably high level, or titer, in their peripheral blood within a couple of weeks of the infection.

Collins: What do antibodies tell us about exposure to a virus?

Sharpless: A lot of people with coronavirus are infected without ever knowing it. You can use these antibody assays to try and tell how many people in an area have been infected, that is, you can do a so-called seroprevalence survey.

You could also potentially use these antibody assays to predict someone’s resistance to future infection. If you cleared the infection and established immunity to it, you might be resistant to future infection. That might be very useful information. Maybe you could make a decision about how to go out in the community. So, that part is of intense interest as well, although less scientifically sound at the moment.

Collins: I have a 3D-printed model of SARS-CoV-2 on my desk. It’s sort of a spherical virus that has spike proteins on its surface. Do the antibodies interact with the virus in some specific ways?

Sharpless: Yes, antibodies are shaped like the letter Y. They have two binding domains at the head of each Y that will recognize something about the virus. We find antibodies in the peripheral blood that recognize either the virus nucleocapsid, which is the structural protein on the inside; or the spikes, which stick out and give coronavirus its name. We know now that about 99 percent of people who get infected with the virus will develop antibodies eventually. Most of those antibodies that you can detect to the spike proteins will be neutralizing, which means they can kill the virus in a laboratory experiment. We know from other viruses that, generally, having neutralizing antibodies is a promising sign if you want to be immune to that virus in the future.

Collins: Are COVID-19 antibodies protective? Are there reports of people who’ve gotten better, but then were re-exposed and got sick again?

Sharpless: It’s controversial. People can shed the virus’s nucleic acid [genetic material], for weeks or even more than a month after they get better. So, if they have another nucleic acid test it could be positive, even though they feel better. Often, those people aren’t making a lot of live virus, so it may be that they never stopped shedding the virus. Or it may be that they got re-infected. It’s hard to understand what that means exactly. If you think about how many people worldwide have had COVID-19, the number of legitimate possible reinfection cases is in the order of a handful. So, it’s a pretty rare event, if it happens at all.

Collins: For somebody who does have the antibodies, who apparently was previously infected, do they need to stop worrying about getting exposed? Can they can do whatever they want and stop worrying about distancing and wearing masks?

Sharpless: No, not yet. To use antibodies to predict who’s likely to be immune, you’ve got to know two things.

First, can the tests actually measure antibodies reliably? I think there are assays available to the public that are sufficiently good for asking this question, with an important caveat. If you’re trying to detect something that’s really rare in a population, then any test is going to have limitations. But if you’re trying to detect something that’s more common, as the virus was during the recent outbreak in Manhattan, I think the tests are up to the task.

Second, does the appearance of an antibody in the peripheral blood mean that you’re actually immune or you’re just less likely to get the virus? We don’t know the answer to that yet.

Collins: Let’s be optimistic, because it sounds like there’s some evidence to support the idea that people who develop these antibodies are protected against infection. It also sounds like the tests, at least some of them, are pretty good. But if there is protection, how long would you expect it to last? Is this one of those things where you’re all set for life? Or is this going to be something where somebody’s had it and might get it again two or three years from now, because the immunity faded away?

Sharpless: Since we have no direct experience with this virus over time, it’s hard to answer. The potential for this cell-based humoral immunity to last for a while is there. For some viruses, you have a long-lasting antibody protection after infection; for other viruses, not so much.

So that’s the unknown thing. Is immunity going to last for a while? Of course, if one were to bring up the topic of vaccines, that’s very important to know, because you would want to know how often one would have to give that vaccine, even under optimal circumstances.

Collins: Yes, our conversation about immunity is really relevant to the vaccines we’re trying to develop right now. Will these vaccines be protective for long periods of time? We sure hope so, but we’ve got to look carefully at the issue. Let’s come back, though, to the actual performance of the tests. The NCI has been right in the middle of trying to do this kind of validation. How did that happen, and how did that experience go?

Sharpless: Yes, I think one might ask: why is the National Cancer Institute testing antibody kits for the FDA? It is unusual, but certainly not unheard of, for NCI to take up problems like this during a time of a national emergency. During the HIV era, NCI scientists, along with others, identified the virus and did one of the first successful compound screens to find the drug AZT, one of the first effective anti-HIV therapies.

NCI’s Frederick National Lab also has a really good serology lab that had been predominantly working on human papillomavirus (HPV). When the need arose for serologic testing a few months ago, we pivoted that lab to a coronavirus serology lab. It took us a little while, but eventually we rounded up everything you needed to create positive and negative reference panels for antibody testing.

At that time, the FDA had about 200 manufacturers making serology tests that hoped for approval to sell. The FDA wanted some performance testing of those assays by a dispassionate third party. The Frederick National Lab seemed like the ideal place, and the manufacturers started sending us kits. I think we’ve probably tested on the order of 20 so far. We give those data back to the FDA for regulatory decision making. They’re putting all the data online.

Collins: How did it look? Are these all good tests or were there some clunkers?

Sharpless: There were some clunkers. But we were pleased to see that some of the tests appear to be really good, both in our hands and those of other groups, and have been used in thousands of patients.

There are a few tests that have sensitivities that are pretty high and specificities well over 99 percent. The Roche assay has a 99.8 percent specificity claimed on thousands of patients, and for the Mt. Sinai assay developed and tested by our academic collaborators in a panel of maybe 4,000 patients, they’re not sure they’ve ever had a false positive. So, there are some assays out there that are good.

Collins: There’s been talk about how there will soon be monoclonal antibodies directed against SARS-CoV-2. How are those derived?

Sharpless: They’re picked, generally, for appearing to have neutralizing activity. When a person makes antibodies, they don’t make one antibody to a pathogen. They make a whole family of them. And those can be individually isolated, so you can know which antibodies made by a convalescent individual really have virus-neutralizing capacity. That portion of the antibody that recognizes the virus can be engineered into a manufacturing platform to make monoclonal antibodies. Monoclonal means one kind of antibody. That approach has worked for other infectious diseases and is an interesting idea here too.

Collins: I can say a bit about that, because we are engaged in a partnership with industry and FDA called Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV). One of the hottest ideas right now is monoclonal antibodies, and we’re in the process of devising a master protocol, one for outpatients and one for inpatients.

Janet Woodcock of Operation Warp Speed tells me 21 companies are developing monoclonal antibodies. While doing these trials, we’d love to do comparisons, which is why it’s good to have an organization like ACTIV to bring everybody together, making sure you’re using the same endpoints and the same laboratory measures. I think that, maybe even by late summer, we might have some results. For people who are looking at what’s the next most-hopeful therapeutic option for people who are really sick with COVID-19, so far we have remdesivir. It helps, but it’s not a home run. Maybe monoclonal antibodies will be the next thing that really gives a big boost in survival. That would be the hope.

Ned, let me ask you one final question about herd, or group, immunity. One hears a bit about that in terms of how we are all going to get past this COVID-19 pandemic. What’s that all about?

Sharpless: Herd immunity is when a significant portion of the population is immune to a pathogen, then that pathogen will die out in the population. There just aren’t enough susceptible people left to infect. What the threshold is for herd immunity depends on how infectious the virus is. For a highly infectious virus, like measles, maybe up to 90 percent of the population must be immune to get herd immunity. Whereas for other less-infectious viruses, it may only be 50 percent of the population that needs to be immune to get herd immunity. It’s a theoretical thing that makes some assumptions, such as that everybody’s health status is the same and the population mixes perfectly every day. Neither of those are true.

How well that actual predictive number will work for coronavirus is unknown. The other thing that’s interesting is a lot of that work has been based on vaccines, such as what percentage do you have to vaccinate to get herd immunity? But if you get to herd immunity by having people get infected, so-called natural herd immunity, that may be different. You would imagine the most susceptible people get infected soonest, and so the heterogeneity of the population might change the threshold calculation.

The short answer is nobody wants to find out. No one wants to get to herd immunity for COVID-19 through natural herd immunity. The way you’d like to get there is with a vaccine that you then could apply to a large portion of the population, and have them acquire immunity in a more safe and controlled manner. Should we have an efficacious vaccine, this question will loom large: how many people do we need to vaccinate to really try and protect vulnerable populations?

Collins: That’s going to be a really critical question for the coming months, as the first large-scale vaccine trials get underway in July, and we start to see how they work and how successful and safe they are. But I’m also worried seeing some reports that 1 out of 5 Americans say they wouldn’t take a vaccine. It would be truly a tragedy if we have a safe and effective vaccine, but we don’t get enough uptake to achieve herd immunity. So, we’ve got some work to do on all fronts, that’s for sure.

Ned, I want to thank you for sharing all this information about antibodies and serologies and other things, as well as thank you for your hard work with all your amazing NCI colleagues.

Sharpless: Thanks for having me.

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The Challenge of Tracking COVID-19’s Stealthy Spread

Dr. Francis Collins — Thu, 23 Apr 2020 14:54:35 -0400

As the nation looks with hope toward controlling the coronavirus 2019 disease pandemic, researchers are forging ahead with efforts to develop and implement strategies to prevent future outbreaks. It sounds straightforward. However, several new studies indicate that containing SARS-CoV-2—the novel coronavirus that causes COVID-19—will involve many complex challenges, not the least of which is figuring out ways to use testing technologies to our best advantage in the battle against this stealthy foe.

The first thing that testing may help us do is to identify those SARS-CoV-2-infected individuals who have no symptoms, but who are still capable of transmitting the virus. These individuals, along with their close contacts, will need to be quarantined rapidly to protect others. These kinds of tests detect viral material and generally analyze cells collected via nasal or throat swabs.

The second way we can use testing is to identify individuals who’ve already been infected with SARS-CoV-2, but who didn’t get seriously ill and can no longer transmit the virus to others. These individuals may now be protected against future infections, and, consequently, may be in a good position to care for people with COVID-19 or who are vulnerable to the infection. Such tests use blood samples to detect antibodies, which are blood proteins that our immune systems produce to attack viruses and other foreign invaders.

A new study, published in Nature Medicine, models what testing of asymptomatic individuals with active SARS-CoV-2 infections may mean for future containment efforts. To develop their model, researchers at China’s Guangzhou Medical University and the University of Hong Kong School of Public Health analyzed throat swabs collected from 94 people who were moderately ill and hospitalized with COVID-19. Frequent in-hospital swabbing provided an objective, chronological record—in some cases, for more than a month after a diagnosis—of each patient’s viral loads and infectiousness.

The model, which also factored in patients’ subjective recollections of when they felt poorly, indicates:

On average, patients became infectious 2.3 days before onset of symptoms.
Their highest level of potential viral spreading likely peaked hours before their symptoms appeared.
Patients became rapidly less infectious within a week, although the virus likely remains in the body for some time.

The researchers then turned to data from a separate, previously published study, which documented the timing of 77 person-to-person transmissions of SARS-CoV-2. Comparing the two data sets, the researchers estimated that 44% of SARS-CoV-2 transmissions occur before people get sick.

Based on this two-part model, the researchers warned that traditional containment strategies (testing only of people with symptoms, contact tracing, quarantine) will face a stiff challenge keeping up with COVID-19. Indeed, they estimated that if more than 30% of new infections come from people who are asymptomatic, and they aren’t tested and found positive until 2 or 3 days later, public health officials will need to track down more than 90% of their close contacts and get them quarantined quickly to contain the virus.

The researchers also suggested alternate strategies for curbing SARS-CoV-2 transmission fueled by people who are initially asymptomatic. One possibility is digital tracing. It involves creating large networks of people who’ve agreed to install a special tracing app on their smart phones. If a phone user tests positive for COVID-19, everyone with the app who happened to have come in close contact with that person would be alerted anonymously and advised to shelter at home.

The NIH has a team that’s exploring various ways to carry out digital tracing while still protecting personal privacy. The private sector also has been exploring technological solutions, with Apple and Google recently announcing a partnership to develop application programming interfaces (APIs) to allow voluntary digital tracing for COVID-19. The rollout of their first API is expected in May.

Of course, all these approaches depend upon widespread access to point-of-care testing that can give rapid results. The NIH is developing an ambitious program to accelerate the development of such testing technologies; stay tuned for more information about this in a forthcoming post.

The second crucial piece of the containment puzzle is identifying those individuals who’ve already been infected by SARS-CoV-2, many unknowingly, but who are no longer infectious. Early results from an ongoing study on residents in Los Angeles County indicated that approximately 4.1% tested positive for antibodies against SARS-CoV-2. That figure is much higher than expected based on the county’s number of known COVID-19 cases, but jibes with preliminary findings from a different research group that conducted antibody testing on residents of Santa Clara County, California.

Still, it’s important to keep in mind that SARS-CoV-2 antibody tests are just in the development stage. It’s possible some of these results might represent false positives—perhaps caused by antibodies to some other less serious coronavirus that’s been in the human population for a while.

More work needs to be done to sort this out. In fact, the NIH’s National Institute of Allergy and Infectious Diseases, which is our lead institute for infectious disease research, recently launched a study to help gauge how many adults in the United States with no confirmed history of a SARS-CoV-2 infection have antibodies to the virus. In this investigation, researchers will collect and analyze blood samples from as many as 10,000 volunteers to get a better picture of SARS-CoV-2’s prevalence and potential to spread within our country.

There’s still an enormous amount to learn about this major public health threat. In fact, NIAID just released its strategic plan for COVID-19 to outline its research priorities. The plan provides more information about the challenges of tracking SARS-CoV-2, as well as about efforts to accelerate research into possible treatments and vaccines. Take a look.

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Genomic Study Points to Natural Origin of COVID-19

Dr. Francis Collins — Wed, 08 Apr 2020 15:40:42 -0400

No matter where you go online these days, there’s bound to be discussion of coronavirus disease 2019, or COVID-19. Some folks are even making outrageous claims that the new coronavirus causing the pandemic was engineered in a lab and deliberately released to make people sick. A new study debunks such claims by providing scientific evidence that this novel coronavirus arose naturally.

The reassuring findings are the result of genomic analyses conducted by an international research team, partly supported by NIH. In their study in the journal Nature Medicine, Kristian Andersen, Scripps Research Institute, La Jolla, CA; Robert Garry, Tulane University School of Medicine, New Orleans; and their colleagues used sophisticated bioinformatic tools to compare publicly available genomic data from several coronaviruses, including the new one that causes COVID-19.

The researchers began by homing in on the parts of the coronavirus genomes that encode the spike proteins that give this family of viruses their distinctive crown-like appearance. (By the way, “corona” is Latin for “crown.”) All coronaviruses rely on spike proteins to infect other cells. But, over time, each coronavirus has fashioned these proteins a little differently, and the evolutionary clues about these modifications are spelled out in their genomes.

The genomic data of the new coronavirus responsible for COVID-19 show that its spike protein contains some unique adaptations. One of these adaptations provides special ability of this coronavirus to bind to a specific protein on human cells called angiotensin converting enzyme (ACE2). A related coronavirus that causes severe acute respiratory syndrome (SARS) in humans also seeks out ACE2.

Existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions, likely because of natural selection on ACE2 that enabled the virus to take advantage of a previously unidentified alternate binding site. Researchers said this provides strong evidence that that new virus was not the product of purposeful manipulation in a lab. In fact, any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular conformation for a spike protein.

The researchers went on to analyze genomic data related to the overall molecular structure, or backbone, of the new coronavirus. Their analysis showed that the backbone of the new coronavirus’s genome most closely resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, the region that binds ACE2 resembles a novel virus found in pangolins, a strange-looking animal sometimes called a scaly anteater. This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature. If the new coronavirus had been manufactured in a lab, scientists most likely would have used the backbones of coronaviruses already known to cause serious diseases in humans.

So, what is the natural origin of the novel coronavirus responsible for the COVID-19 pandemic? The researchers don’t yet have a precise answer. But they do offer two possible scenarios.

In the first scenario, as the new coronavirus evolved in its natural hosts, possibly bats or pangolins, its spike proteins mutated to bind to molecules similar in structure to the human ACE2 protein, thereby enabling it to infect human cells. This scenario seems to fit other recent outbreaks of coronavirus-caused disease in humans, such as SARS, which arose from cat-like civets; and Middle East respiratory syndrome (MERS), which arose from camels.

The second scenario is that the new coronavirus crossed from animals into humans before it became capable of causing human disease. Then, as a result of gradual evolutionary changes over years or perhaps decades, the virus eventually gained the ability to spread from human-to-human and cause serious, often life-threatening disease.

Either way, this study leaves little room to refute a natural origin for COVID-19. And that’s a good thing because it helps us keep focused on what really matters: observing good hygiene, practicing social distancing, and supporting the efforts of all the dedicated health-care professionals and researchers who are working so hard to address this major public health challenge.

Finally, next time you come across something about COVID-19 online that disturbs or puzzles you, I suggest going to FEMA’s new Coronavirus Rumor Control web site. It may not have all the answers to your questions, but it’s definitely a step in the right direction in helping to distinguish rumors from facts.

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To Beat COVID-19, Social Distancing is a Must

Dr. Francis Collins — Mon, 23 Mar 2020 14:01:45 -0400

Even in less challenging times, many of us try to avoid close contact with someone who is sneezing, coughing, or running a fever to avoid getting sick ourselves. Our attention to such issues has now been dramatically heightened by the emergence of a novel coronavirus causing a pandemic of an illness known as COVID-19.

Many have wondered if we couldn’t simply protect ourselves by avoiding people with symptoms of respiratory illness. Unfortunately, the answer is no. A new study shows that simply avoiding symptomatic people will not go far enough to curb the COVID-19 pandemic. That’s because researchers have discovered that many individuals can carry the novel coronavirus without showing any of the typical symptoms of COVID-19: fever, dry cough, and shortness of breath. But these asymptomatic or only mildly ill individuals can still shed virus and infect others.

This conclusion adds further weight to the recent guidance from U.S. public health experts: what we need most right now to slow the stealthy spread of this new coronavirus is a full implementation of social distancing. What exactly does social distancing mean? Well, for starters, it is recommended that people stay at home as much as possible, going out only for critical needs like groceries and medicines, or to exercise and enjoy the outdoors in wide open spaces. Other recommendations include avoiding gatherings of more than 10 people, no handshakes, regular handwashing, and, when encountering someone outside of your immediate household, trying to remain at least 6 feet apart.

These may sound like extreme measures. But the new study by NIH-funded researchers, published in the journal Science, documents why social distancing may be our best hope to slow the spread of COVID-19. Here are a few highlights of the paper, which looks back to January 2020 and mathematically models the spread of the coronavirus within China:

For every confirmed case of COVID-19, there are likely another five to 10 people with undetected infections.
Although they are thought to be only about half as infectious as individuals with confirmed COVID-19, individuals with undetected infections were so prevalent in China that they apparently were the infection source for 86 percent of confirmed cases.
After China established travel restrictions and social distancing, the spread of COVID-19 slowed considerably.

The findings come from a small international research team that included NIH grantee Jeffrey Shaman, Columbia University Mailman School of Public Health, New York. The team developed a computer model that enabled researchers to simulate the time and place of infections in a grid of 375 Chinese cities. The researchers did so by combining existing data on the spread of COVID-19 in China with mobility information collected by a location-based service during the country’s popular 40-day Spring Festival, when travel is widespread.

As these new findings clearly demonstrate, each of us must take social distancing seriously in our daily lives. Social distancing helped blunt the pandemic in China, and it will work in other nations, including the United States. While many Americans will likely spend weeks working and studying from home and practicing other social distancing measures, the stakes remain high. If this pandemic isn’t contained, this novel coronavirus could well circulate around the globe for years to come, at great peril to us and our loved ones.

As we commit ourselves to spending more time at home, progress continues to be made in using the power of biomedical research to combat this novel coronavirus. A notable step this week was the launch of an early-stage human clinical trial of an investigational vaccine, called mRNA-1273, to protect against COVID-19. The vaccine candidate was developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and their collaborators at the biotechnology company Moderna, Inc., in Cambridge, Massachusetts.

This Phase 1 NIAID-supported trial will look at the safety of the vaccine—which cannot cause infection because it is made of RNA, not the whole coronavirus—in 45 healthy adults. The first volunteer was injected this past Monday at Kaiser Permanente Washington Health Research Institute, Seattle. If all goes well and larger follow-up clinical studies establish the vaccine’s safety and efficacy, it will then be necessary to scale up production to make millions of doses. While initiating this trial in record time is reason for hope, it is important to be realistic about all of the steps that still remain. If the vaccine candidate proves safe and effective, it will likely take at least 12–18 months before it would be widely available.

In the meantime, social distancing remains one of the best weapons we have to slow the silent spread of this virus and flatten the curve of the COVID-19 pandemic. This will give our health-care professionals, hospitals, and other institutions more valuable time to prepare, protect themselves, and aid the many people whose lives may be on the line from this coronavirus.

Importantly, saving lives from COVID-19 requires all of us—young, old and in-between—to take part. Healthy young people, whose risk of dying from coronavirus is not zero but quite low, might argue that they shouldn’t be constrained by social distancing. However, the research highlighted here demonstrates that such individuals are often the unwitting vector for a dangerous virus that can do great harm—and even take the lives of older and more vulnerable people. Think about your grandparents. Then skip the big gathering. We are all in this together.

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Discovering the Brain’s Nightly 'Rinse Cycle'

Dr. Francis Collins — Mon, 16 Mar 2020 15:04:07 -0400

Getting plenty of deep, restful sleep is essential for our physical and mental health. Now comes word of yet another way that sleep is good for us: it triggers rhythmic waves of blood and cerebrospinal fluid (CSF) that appear to function much like a washing machine’s rinse cycle, which may help to clear the brain of toxic waste on a regular basis.

The video above uses functional magnetic resonance imaging (fMRI) to take you inside a person’s brain to see this newly discovered rinse cycle in action. First, you see a wave of blood flow (red, yellow) that’s closely tied to an underlying slow-wave of electrical activity (not visible). As the blood recedes, CSF (blue) increases and then drops back again. Then, the cycle—lasting about 20 seconds—starts over again.

The findings, published recently in the journal Science, are the first to suggest that the brain’s well-known ebb and flow of blood and electrical activity during sleep may also trigger cleansing waves of blood and CSF. While the experiments were conducted in healthy adults, further study of this phenomenon may help explain why poor sleep or loss of sleep has previously been associated with the spread of toxic proteins and worsening memory loss in people with Alzheimer’s disease.

In the new study, Laura Lewis, Boston University, MA, and her colleagues at the Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston. recorded the electrical activity and took fMRI images of the brains of 13 young, healthy adults as they slept. The NIH-funded team also built a computer model to learn more about the fluid dynamics of what goes on in the brain during sleep. And, as it turns out, their sophisticated model predicted exactly what they observed in the brains of living humans: slow waves of electrical activity followed by alternating waves of blood and CSF.

Lewis says her team is now working to come up with even better ways to capture CSF flow in the brain during sleep. Currently, people who volunteer for such experiments have to be able to fall asleep while wearing an electroencephalogram (EEG) cap inside of a noisy MRI machine—no easy feat. The researchers are also recruiting older adults to begin exploring how age-related changes in brain activity during sleep may affect the associated fluid dynamics.

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Structural Biology Points Way to Coronavirus Vaccine

Dr. Francis Collins — Wed, 04 Mar 2020 12:53:34 -0500

The recent COVID-19 outbreak of a novel type of coronavirus that began in China has prompted a massive global effort to contain and slow its spread. Despite those efforts, over the last month the virus has begun circulating outside of China in multiple countries and territories.

Cases have now appeared in the United States involving some affected individuals who haven’t traveled recently outside the country. They also have had no known contact with others who have recently arrived from China or other countries where the virus is spreading. The NIH and other U.S. public health agencies stand on high alert and have mobilized needed resources to help not only in its containment, but in the development of life-saving interventions.

On the treatment and prevention front, some encouraging news was recently reported. In record time, an NIH-funded team of researchers has created the first atomic-scale map of a promising protein target for vaccine development. This is the so-called spike protein on the new coronavirus that causes COVID-19. As shown above, a portion of this spiky surface appendage (green) allows the virus to bind a receptor on human cells, causing other portions of the spike to fuse the viral and human cell membranes. This process is needed for the virus to gain entry into cells and infect them.

Preclinical studies in mice of a candidate vaccine based on this spike protein are already underway at NIH’s Vaccine Research Center, part of the National Institute of Allergy and Infectious Diseases. An early-stage phase I clinical trial of this vaccine in people is expected to begin within weeks. But there will be many more steps after that to test safety and efficacy, and then to scale up to produce millions of doses. Even though this timetable will potentially break all previous speed records, a safe and effective vaccine will take at least another year to be ready for widespread deployment.

Coronaviruses are a large family of viruses, including some that cause “the common cold” in healthy humans. In fact, these viruses are found throughout the world and account for up to 30 percent of upper respiratory tract infections in adults.

This outbreak of COVID-19 marks the third time in recent years that a coronavirus has emerged to cause severe disease and death in some people. Earlier coronavirus outbreaks included SARS (severe acute respiratory syndrome), which emerged in late 2002 and disappeared two years later, and MERS (Middle East respiratory syndrome), which emerged in 2012 and continues to affect people in small numbers.

Soon after COVID-19 emerged, the new coronavirus, which is closely related to SARS, was recognized as its cause. NIH-funded researchers including Jason McLellan, an alumnus of the VRC and now at The University of Texas at Austin, were ready. They’d been studying coronaviruses in collaboration with NIAID investigators for years, with special attention to the spike proteins.

Just two weeks after Chinese scientists reported the first genome sequence of the virus, McLellan and his colleagues designed and produced samples of its spike protein. Importantly, his team had earlier developed a method to lock coronavirus spike proteins into a shape that makes them both easier to analyze structurally via the high-resolution imaging tool cryo-electron microscopy and to use in vaccine development efforts.

After locking the spike protein in the shape it takes before fusing with a human cell to infect it, the researchers reconstructed its atomic-scale 3D structural map in just 12 days. Their results, published in Science, confirm that the spike protein on the virus that causes COVID-19 is quite similar to that of its close relative, the SARS virus. It also appears to bind human cells more tightly than the SARS virus, which may help to explain why the new coronavirus appears to spread more easily from person to person, mainly by respiratory transmission.

McLellan’s team and his NIAID VRC counterparts also plan to use the stabilized spike protein as a probe to isolate naturally produced antibodies from people who’ve recovered from COVID-19. Such antibodies might form the basis of a treatment for people who’ve been exposed to the virus, such as health care workers.

The NIAID is now working with the biotechnology company Moderna, Cambridge, MA, to use the latest findings to develop a vaccine candidate using messenger RNA (mRNA), molecules that serve as templates for making proteins. The goal is to direct the body to produce a spike protein in such a way to elicit an immune response and the production of antibodies. An early clinical trial of the vaccine in people is expected to begin in the coming weeks. Other vaccine candidates are also in preclinical development.

Meanwhile, the first clinical trial in the U.S. to evaluate an experimental treatment for COVID-19 is already underway at the University of Nebraska Medical Center’s biocontainment unit. The NIH-sponsored trial will evaluate the safety and efficacy of the experimental antiviral drug remdesivir in hospitalized adults diagnosed with COVID-19. The first participant is an American who was repatriated after being quarantined on the Diamond Princess cruise ship in Japan.

As noted, the risk of contracting COVID-19 in the United States is currently low, but the situation is changing rapidly. One of the features that makes the virus so challenging to stay in front of is its long latency period before the characteristic flu-like fever, cough, and shortness of breath manifest. In fact, people infected with the virus may not show any symptoms for up to two weeks, allowing them to pass it on to others in the meantime. You can track the reported cases in the United States on the Centers for Disease Control and Prevention’s website.

As the outbreak continues over the coming weeks and months, you can be certain that NIH and other U.S. public health organizations are working at full speed to understand this virus and to develop better diagnostics, treatments, and vaccines.

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Why When You Eat Might Be as Important as What You Eat

Dr. Francis Collins — Tue, 10 Dec 2019 12:25:59 -0500

About 1 in 3 American adults have metabolic syndrome, a group of early warning signs for increased risk of type 2 diabetes, heart disease, and stroke. To help avoid such health problems, these folks are often advised to pay close attention to the amount and type of foods they eat. And now it seems there may be something else to watch: how food intake is spaced over a 24-hour period.

In a three-month pilot study, NIH-funded researchers found that when individuals with metabolic syndrome consumed all of their usual daily diet within 10 hours—rather than a more customary span of about 14 hours—their early warning signs improved. Not only was a longer stretch of daily fasting associated with moderate weight loss, in some cases, it was also tied to lower blood pressure, lower blood glucose levels, and other improvements in metabolic syndrome.

The study, published in Cell Metabolism, is the result of a joint effort by Satchidananda Panda, Salk Institute for Biological Sciences, La Jolla, CA, and Pam R. Taub, University of California, San Diego. It was inspired by Panda’s earlier mouse studies involving an emerging dietary intervention, called time-restricted eating (TRE), which attempts to establish a consistent daily cycle of feeding and fasting to create more stable rhythms for the body’s own biological clock.

But would observations in mice hold true for humans? To find out, Panda joined forces with Taub, a cardiologist and physician-scientist. The researchers enlisted 19 men and women with metabolic syndrome, defined as having three or more of five specific risk factors: high fasting blood glucose, high blood pressure, high triglyceride levels, low “good” cholesterol, and/or extra abdominal fat. Most participants were obese and taking at least one medication to help manage their metabolic risk factors.

In the study, participants followed one rule: eat anything that you want, just do so over a 10-hour period of your own choosing. So, for the next three months, these folks logged their eating times and tracked their sleep using a special phone app created by the research team. They also wore activity and glucose monitors.

By the pilot study’s end, participants following the 10-hour limitation had lost on average 3 percent of their weight and about 3 percent of their abdominal fat. They also lowered their cholesterol and blood pressure. Although this study did not find 10-hour TRE significantly reduced blood glucose levels in all participants, those with elevated fasting blood glucose did have improvement. In addition, participants reported other lifestyle improvements, including better sleep.

The participants generally saw their metabolic health improve without skipping meals. Most chose to delay breakfast, waiting about two hours after they got up in the morning. They also ate dinner earlier, about three hours before going to bed—and then did no late night snacking.

After the study, more than two-thirds reported that they stuck with the 10-hour eating plan at least part-time for up to a year. Some participants were able to cut back or stop taking cholesterol and/or blood-pressure-lowering medications.

Following up on the findings of this small study, Taub will launch a larger NIH-supported clinical trial involving 100 people with metabolic syndrome. Panda is now exploring in greater detail the underlying biology of the metabolic benefits observed in the mice following TRE.

For people looking to improve their metabolic health, it’s a good idea to consult with a doctor before making significant changes to one’s eating habits. But the initial data from this study indicate that, in addition to exercising and limiting portion size, it might also pay to watch the clock.

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It's Time to End the 'Manel' Tradition of All-Male Speaking Panels

Dr. Francis Collins — Thu, 13 Jun 2019 13:22:27 -0400

The National Institutes of Health is committed to changing the culture and climate of biomedical research to create an inclusive and diverse workforce. The recent report by the National Academy of Sciences, Engineering and Medicine, “Sexual Harassment of Women: Climate, Culture, and Consequence in Academic Science, Engineering, and Medicine,” identified the critical role that scientific leaders must play to combat cultural forces that tolerate gender harassment and limit the advancement of women. These concerns also are highly relevant to other groups underrepresented in science. It is not enough to give lip service to equality; leaders must demonstrate their commitment through their actions.

Toward that end, I want to send a clear message of concern: it is time to end the tradition in science of all-male speaking panels, sometimes wryly referred to as “manels.” Too often, women and members of other groups underrepresented in science are conspicuously missing in the marquee speaking slots at scientific meetings and other high-level conferences. Starting now, when I consider speaking invitations, I will expect a level playing field, where scientists of all backgrounds are evaluated fairly for speaking opportunities. If that attention to inclusiveness is not evident in the agenda, I will decline to take part. I challenge other scientific leaders across the biomedical enterprise to do the same.

The diversity of bright and talented minds engaged in biomedical research has come a long way – and our public engagements need to catch up. Breaking up the subtle (and sometimes not so subtle) bias that is preventing women and other groups underrepresented in science from achieving their rightful place in scientific leadership must begin at the top.

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Possible Explanation for Why Some People Get More Colds

Dr. Francis Collins, National Institutes of Health — Wed, 17 Oct 2018 09:00:00 -0400

Colds are just an occasional nuisance for many folks, but some individuals seem to come down with them much more frequently. Now, NIH-funded researchers have uncovered some new clues as to why.

In their study, the researchers found that the cells that line our airways are quite adept at defending against cold-causing rhinoviruses. But there’s a tradeoff. When these cells are busy defending against tissue damage due to cigarette smoke, pollen, pollutants, and/or other airborne irritants, their ability to fend off such viruses is significantly reduced.

The new findings may open the door to better strategies for preventing the common cold, as well as other types of respiratory tract infections caused by non-flu viruses. Even small improvements in prevention could have big implications for our nation’s health and economy. Every year, Americans come down with more than 500 million colds and similar infections, leading to reduced work productivity, medical expenses, and other costs approaching $40 billion.

Over the last decade, evidence shows that people become infected with rhinoviruses much more often than they actually develop cold symptoms. That intrigued Ellen Foxman at Yale University School of Medicine, New Haven, CT. It suggested to her that the body, especially the cells in the nasal passages, must be very good at ridding us of cold viruses.

If that natural process were understood better, Foxman thought it might be possible to encourage respiratory infections to pass unnoticed even more often. Foxman already had a possible clue. Her earlier work showed that how cells respond to viral infections varies with temperature. She suspected that cells lining the cooler nasal passages must operate differently than those lining warmer airways within the lungs.

In the study published in Cell Reports, Foxman and colleagues at Yale, including first author Valia Mihaylova, cultured epithelial cells that line the nasal passages and lungs from healthy donors. They infected them with a rhinovirus or exposed them to small molecules that mimic a viral infection and watched to see how the cells would respond.

The researchers discovered the anti-viral response was stronger in the nasal cells. In contrast, cells taken from the lungs showed a stronger defense against oxidative stress, caused by reactive oxygen molecules produced in the normal course of breathing. As would be expected, lung cells must defend themselves against not only reactive oxygen but also other substances present in air laden with smoke, pollen, or other irritants.

These and other experiments suggested there is a tradeoff between defending against viral infections and other kinds of tissue damage. To take a closer look, the researchers introduced rhinovirus to cells from the nasal passages after they’d been exposed to cigarette smoke. As suspected, those cells showed a greater susceptibility to viral infection.

The findings show that the lining of our airways has effective systems in place to defend against viral infections and protect against other types of damage. But it doesn’t do so well when faced with both challenges at once. The discovery may help to explain why smokers and those with allergies or other chronic conditions tend to get more severe viral infections than other people do.

The hope is these insights will ultimately lead to strategies to improve the body’s natural defenses so that more people stay healthy even after exposure to cold viruses. For now, the best way to keep colds to a minimum is to wash your hands often, don’t smoke, and do your best to stay away from those who are sick.

Dr. Francis Collins was ppointed the 16th Director of NIH by President Barack Obama and confirmed by the Senate. He was sworn in on August 17, 2009. On June 6, 2017. President Donald Trump selected Dr. Collins to continue to serve as the NIH Director.

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How Sleep Resets the Brain

Dr. Francis Collins — Mon, 08 May 2017 08:00:00 -0400

People spend about a third of their lives asleep. When we get too little shut-eye, it takes a toll on attention, learning and memory, not to mention our physical health. Virtually all animals with complex brains seem to have this same need for sleep. But exactly what is it about sleep that’s so essential?

Two NIH-funded studies in mice now offer a possible answer. The two research teams used entirely different approaches to reach the same conclusion: the brain’s neural connections grow stronger during waking hours, but scale back during snooze time. This sleep-related phenomenon apparently keeps neural circuits from overloading, ensuring that mice (and, quite likely humans) awaken with brains that are refreshed and ready to tackle new challenges.

The idea that sleep is required to keep the brain wiring sharp goes back more than a decade. While a fair amount of evidence has emerged to support the hypothesis, its originators Chiara Cirelli and Giulio Tononi of the University of Wisconsin-Madison, set out in their new study to provide some of the first direct visual proof that it’s indeed the case.

As published in the journal Science, the researchers used a painstaking, cutting-edge imaging technique to capture high-resolution pictures of two areas of the mouse’s cerebral cortex, a part of the brain that coordinates incoming sensory and motor information. The technique, called serial scanning 3D electron microscopy, involves repeated scanning of small slices of the brain to produce many thousands of images, allowing the researchers to produce detailed 3D reconstructions of individual neurons.

Their goal was to measure the size of the synapses, where the ends of two neurons connect. Synapses are critical for one neuron to pass signals on to the next, and the strength of those neural connections corresponds to their size.

The researchers measured close to 7,000 synapses in all. Their images show that synapses grew stronger and larger as these nocturnal mice scurried about at night. Then, after 6 to 8 hours of sleep during the day, those synapses shrank by about 18 percent as the brain reset for another night of activity. Importantly, the effects of sleep held when the researchers switched the mice’s schedule, keeping them up and engaged with toys and other objects during the day.

In the second Science report, Richard Huganir and his colleagues at Johns Hopkins University School of Medicine, Baltimore, measured changes in the levels of certain brain proteins with sleep to offer biochemical evidence for this weakening of synapses. Their findings show that levels of protein receptors found on the receiving ends of synapses dropped by 20 percent while their mice slept.

The researchers also show that the protein Homer1a—important in regulating sleep and wakefulness—rises in synapses during a long snooze, playing a critical role in the resetting process. When the protein was lacking, brains didn’t reset properly during sleep. This suggests that Homer1a responds to chemical cues in the brain that signal the need to sleep.

These studies add to prior work that suggests another function of sleep is to allow glial lymphatics in the brain to clear out proteins and other toxins that have deposited during the day. All of this goes to show that a good night’s sleep really can bring clarity. So, the next time you’re struggling to make a decision and someone tells you to “sleep on it”—that might be really good advice.

Francis S. Collins, M.D., Ph.D. is the Director of the National Institutes of Health

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It’s Not Your Imagination: Social Media Is Making Us Lonelier

Dr. Francis Collins — Fri, 14 Apr 2017 07:07:15 -0400

Initially, most of us thought that Facebook, Instagram, Twitter, and other social media applications would help to bring people together. And, yes, in many instances that has been true. Such apps have made it possible—even simple—to catch up with former classmates living thousands of miles away, share a video of your baby’s first steps with relatives near and far, or strike up new acquaintances while discussing the stock market or last night’s ballgame. Yet, a new NIH-funded study suggests that social media may also have the power to make people feel left out and alone.

Based on a nationwide survey of more than 1,700 young adults, researchers found that individuals who were the heaviest users of social media were two to three times more likely to feel socially isolated than those who used little to no social media. And that’s a concern to those of us in the medical field: previous research has linked social isolation to worsening physical and mental health, and even an increased risk of death. In fact, some experts have gone so far as to label loneliness a major public health concern.

The new study, reported in the American Journal of Preventive Medicine, was led by Brian Primack and his colleagues from the University of Pittsburgh. They set out to look specifically at social media use and its possible association with feelings of social isolation in young adults.

To do so, they randomly surveyed 1,787 male and female young adults about their use of 11 popular social media applications. These included Facebook, Twitter, YouTube, LinkedIn, Snapchat, Instagram, and Reddit.

The survey also contained four questions about social isolation, or lacking a sense of social belonging. For each of the four questions, participants selected a number from 1 to 5, corresponding to never, rarely, sometimes, often, and always. Their perceived social isolation was then calculated by adding up the answers to those four questions.

Respondents, who were ages 19 to 32, were quite diverse in their educational level, income, and ethnicity. A little over half were white, with 13 percent African American, 20 percent Hispanic, and 9 percent racially mixed.

Primack and his colleagues found that the top users of social media spent more than two hours per day on the apps, visiting them on average at least 58 times per week. Those who were the most limited users of social media least spent 30 minutes or less clicking on social media each day, with 8 or fewer weekly visits per week.

The researchers found that people who spent the most time on social media were twice as likely to feel more socially isolated. And those who logged onto social media apps several times each day were more than three times as likely as those who rarely used social media to feel more socially isolated.

There’s a chicken-and-the-egg issue here. It’s not really clear which came first: social media use leading to feelings of social isolation—or vice versa. It’s possible that people who feel socially isolated look to social media to help fill the void. Or, it may be that spending hours on social media, rather than on other activities, encourages feelings of isolation and even jealousy. That is, people may read the carefully selected posts of their friends who appear to be having fun, and become resentful of being left out. It may also be some combination of both.

The researchers say they don’t mean to imply that people should drop social media altogether. Social media is a useful tool and, for many of us, it has become an integral part of modern life. But going forward, it will be important to learn how to develop and maintain healthy social media habits that add to, rather than detract from, the quality of our lives. As with many things in life, balance is key.

Francis S. Collins, M.D., Ph.D. is the Director of the National Institutes of Health

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Forgetting More Things? There’s Something You Can Do

Dr. Francis Collins — Thu, 07 Jul 2016 15:05:33 -0400

We all know that exercise is important for a strong and healthy body. Less appreciated is that exercise seems also to be important for a strong and healthy mind, boosting memory and learning, while possibly delaying age-related cognitive decline. How is this so? Researchers have assembled a growing body of evidence that suggests skeletal muscle cells secrete proteins and other factors into the blood during exercise that have a regenerative effect on the brain.

Now, an NIH-supported study has identified a new biochemical candidate to help explore the muscle-brain connection: a protein secreted by skeletal muscle cells called cathepsin B. The study found that levels of this protein rise in the blood of people who exercise regularly, in this case running on a treadmill. In mice, brain cells treated with the protein also exhibited molecular changes associated with the production of new neurons. Interestingly, the researchers found that the memory boost normally provided by exercise is diminished in mice unable to produce cathepsin B.

The findings, published recently in Cell Metabolism, are from a team of researchers led by Hyo Youl Moon and Henriette van Praag of NIH’s National Institute on Aging. The team set out to find proteins that muscle cells secrete during exercise that could be transported to the brain. The researchers began by treating muscle cells in lab dishes with a chemical called AICAR, which mimics the effects of exercise on muscle and boosts running endurance in inactive mice. AICAR treatment also improves brain function in mice in a way that is similar, but not identical, to exercise.

The search produced a short list of potentially important proteins. By comparing their short list to existing data on secreted proteins and changes in gene expression after exercise or AICAR treatment, one protein really stuck out: cathepsin B. This small enzyme is primarily known for its role in the degradation and turnover of peptides and proteins inside of cells. But some cells also secrete cathepsin B, and its extracellular effects are less well understood.

To learn more about cathepsin B and exercise, the researchers turned to mice and found that blood levels of the enzyme rose after they ran regularly for two weeks or more. They also showed that levels of the protein rose in muscle, but not in other organs and tissues. Taken together, the findings suggested that running results specifically in production of cathepsin B in muscle and leads to its secretion into the bloodstream.

The team next turned to genetically engineered mice unable to produce cathepsin B. Unlike normal mice, these mice when exercising no longer produced new neurons in the dentate gyrus, a part of the brain associated with memory. They also showed no improvement with exercise in their spatial memory and ability to navigate a maze in the way that mice typically can.

For cathepsin B to influence the brain, it would first need to cross the blood-brain barrier, which blocks proteins that are too big or have the wrong biochemistry from entering the brain. The researchers injected cathepsin B into mice unable to produce the chemical themselves. Within 15 minutes, they found that the protein had crossed into the brain. They also found that brain cells treated with cathepsin B showed changes in gene expression consistent with the growth of new neurons.

To see if their findings extended beyond cells and mice, the researchers compared cathepsin B levels in people after four months of regular exercise on a treadmill to those who didn’t exercise. The study, conducted in Germany, involved about 40 healthy young adults. They were between the ages of 19 and 34 years old, and about equally divided between men and women.

Sure enough, the study showed a significant increase in blood cathepsin B levels with regular fitness training. They also found a relationship between increases in cathepsin B and the ability of participants to recall and accurately draw a complex assemblage of lines and geometric shapes, which is often used to assess visual memory.

These discoveries on cathepsin B come as something of a surprise. Elevated levels of the enzyme have previously been linked to a wide array of diseases, from cancer to epilepsy. There’s also conflicting evidence about a potential role for cathepsin B in the development of Alzheimer’s disease, and drugs that block the enzyme have been proposed to treat traumatic brain injury, among many other conditions.

And yet, compounds that elevate cathepsin B levels in mouse models of Alzheimer’s disease have been neuroprotective. As van Praag notes, those findings are consistent with animal research showing that physical activity may prevent or delay the onset of Alzheimer’s disease.

Clearly, many questions about cathepsin B and its role in the brain and the rest of the body remain. Few prior studies have focused on the function of this protein in people who are generally healthy. The researchers hope to continue learning about how cathepsin B makes its way into the brain and influences the development of new neural connections once there. Whatever they find, this study adds another insight to the evidence that’s coming from many directions: it really does pay to exercise.

Francis S. Collins, M.D., Ph.D. is the Director of the National Institutes of Health (NIH).

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Expanding the Reach of Precision Medicine

Dr. Francis Collins, National Institutes of Health — Fri, 25 Sep 2015 16:00:00 -0400

Readers of the NIH Director’s Blog know how excited I am about the potential of precision medicine for revolutionizing efforts to treat disease and improve human health. So, it stands to reason that I’m delighted by the positive reactions of researchers, health professionals, and the public to a much-anticipated report from the Precision Medicine Initiative Working Group of the Advisory Committee to the NIH Director. Topping the report’s list of visionary recommendations? Build a national research cohort of 1 million or more Americans over the next three to four years to expand knowledge and practice of precision medicine.

When the president announced PMI during his 2015 State of the Union address, he envisioned a precise new era in medicine in which every patient receives the right treatment at the right time — an era in which health care professionals have the resources at hand to take into account individual differences in genes, environments, and lifestyles that contribute to disease. To achieve this, PMI’s national research cohort would tap into recent advances in science, technology and research participation policies to build the knowledge base needed to develop individualized care for all diseases and conditions.

The Working Group’s report was accepted unanimously and enthusiastically by the Advisory Committee to the Director last week. Based on that response, I formally accepted the recommendations and announced we would move into the implementation phase. To get a better feel for what Americans are thinking about PMI, I took part this week in a Twitter chat co-hosted by NIH and the White House Office of Science and Technology Policy. Also participating were Josephine Briggs, director of NIH’s National Center for Complementary and Integrative Health, who is serving as interim director of PMI Cohort Program, while a search is underway for a permanent chief; and two of the Working Group’s three co-chairs, NIH Deputy Director for Science, Outreach and Policy Kathy Hudson and Bray Patrick-Lake, director of stakeholder engagement for the Clinical Trials Transformation Initiative at Duke University.

The Twitter chat proved quite popular, attaining a reach of more than 76 million potential impressions and attracting some 2,975 comments from 480 participants in 36 states. For a taste of the discussion, here’s a quick sample of what some of those folks were saying:

“Another remarkable aspect of #PMINetwork is appreciation of confluence of biology, environment, context, circumstances. The whole gemisch” @hmkyale

“Improved #communications, education can end #healthcare fragmentation so #PrecisionMedicine can fulfill its promise.” @Betsy_RSHC

“When can we start enrolling? I’m ready! #PMINetwork.” @trluperchio

In addition to the buzz on social media, the Working Group’s framework for the research cohort component of PMI attracted the attention of both mainstream and scientific media. While the news coverage was generally good, there remain a few misconceptions I’d like to clear up. At least one headline said that NIH planned to build a “genetic database.” While it’s true that genetic analysis will be a key part of PMI, the cohort will involve far more than simply studying DNA. In fact, the cohort will use a variety of innovative tools and technologies to gather information on participants’ behaviors, lifestyles, and environmental exposures as a means to better define how these factors influence health and disease. For example, it’s easy to envision using smartphone apps or other mobile health devices to monitor participants’ physical activity, track their sleep patterns, measure various aspects of cardiovascular function and metabolism, and even detect changes in the microorganisms living in or on their bodies. It’s also a good bet that a lot of data will be gathered to improve understanding of the aging process, as well as health differences between males and females.

Some have asked what will be done to safeguard the privacy of people who volunteer for the PMI research cohort, which is expected to start enrolling participants sometime next year. This responsibility is a high priority for the project. Last month, the White House completed its public comment period on PMI’s proposed privacy and trust principles, which are aimed at protecting participants’ personal data while at the same time making essential research data broadly available to qualified scientists.

Finally, I’d like to extend my sincere thanks to all 19 members of the PMI Working Group, especially its three hardworking co-chairs: Dr. Hudson, Ms. Patrick-Lake, and Dr. Rick Lifton of Yale University School of Medicine. It’s also been fantastic for NIH to partner on PMI planning with the White House’s Office of the National Coordinator for Health Information and the Food and Drug Administration. In fact, the recently named nominee for FDA commissioner, Dr. Robert Califf, was an ex officio member of the PMI Working Group. With these and so many more great minds involved in drawing up this bold blueprint for PMI, I look forward to the day—hopefully, in the very near future—when NIH can set to work turning this exciting vision into extraordinary opportunities for moving precision medicine into all areas of health.

(Image via alexmillos/Shutterstock.com)

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President’s Visit to NIH Highlights Research on Ebola

Dr. Francis Collins, National Institutes of Health — Thu, 04 Dec 2014 16:00:00 -0500

On Tuesday, we had the great honor of welcoming President Obama to the campus of the National Institutes of Health in Bethesda, Maryland—to see firsthand the progress that biomedical research is making against Ebola virus disease. The president toured the NIH Vaccine Research Center and met with scientists who are working hard to develop ways to combat this deadly virus that continues to devastate West Africa. And, in a speech before a packed auditorium at the NIH Clinical Center, the president praised the contributions of NIH staff. He also emphasized the need for emergency congressional authorization of resources to ensure that our nation’s research and public health efforts against Ebola will lead as quickly as possible to an end to this devastating outbreak.

The president heard about many encouraging advances against Ebola during his visit here, and I’d like to share a couple with you now. I think these examples—one about a vaccine and one about a treatment—speak to the extraordinary ways in which scientists from different fields, disciplines, and organizations are pulling together to tackle this urgent disease threat.

The first piece of good news relates to efforts to prevent Ebola virus disease: we recently received promising, early results from the initial clinical trial of a candidate Ebola vaccine, conducted here at the NIH Clinical Center. In a study published last week in The New England Journal of Medicine, researchers reported that this Phase I trial established that the vaccine was well tolerated—and that it produced measurable immune responses—in all 20 healthy adult volunteers who received it. Based on these preliminary results, we plan to keep moving the vaccine toward the larger, randomized clinical studies necessary to determine whether it is effective in preventing Ebola infection.

The vaccine used in this trial was co-developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases and the British-based pharmaceutical firm, GlaxoSmithKline. It must be emphasized that this candidate vaccine is not made from the whole Ebola virus and, thus, cannot cause Ebola virus disease. Rather, it contains snippets of genetic material from two major strains of the Ebola virus, Sudan and Zaire. This noninfectious genetic material is delivered by a carrier virus that causes the common cold in chimpanzees, but does not make humans sick.

Let me double back and tell you a bit more about the study. All 20 of the volunteers were between the ages of 18 and 50. Half received an intramuscular injection of vaccine at a lower dose, and the rest received the same vaccine at a higher dose. At two and four weeks after vaccination, the researchers drew blood from the volunteers to determine whether anti-Ebola antibodies were generated. All 20 volunteers had generated potentially protective antibodies within four weeks of receiving the vaccine, but the antibody levels were higher in those who received the higher dose vaccine. Another important observation is that the NIAID/GSK vaccine induced memory immune cells, called T-cells, in many of the volunteers, including the production of CD8 T cells, which may be a key part of immune protection against the Ebola virus.

The second area of research progress involves a potential treatment for Ebola virus disease, specifically, the investigational drug ZMapp. This drug, which NIAID has supported and collaborated with Mapp Biopharmaceutical Inc. of San Diego, is a cocktail of three highly purified monoclonal antibodies, or protective immune proteins, known to target the virus.

ZMapp was in the news last summer when it was administered on a compassionate basis to several individuals who were seriously ill with Ebola virus disease. While most (but not all) of those who received ZMapp survived, we do not know if the drug played any role in these positive outcomes. To gather more solid scientific evidence, NIH has a strong interest in conducting clinical studies to better evaluate the drug’s safety and efficacy.

There also is an important basic research question: Where exactly do ZMapp’s three monoclonal antibodies bind to the Ebola virus and possibly neutralize it? Researchers at The Scripps Research Institute in La Jolla, California, say they now have the answer. Using a high-resolution imaging technique, called single-particle electron microscopy, the researchers recently mapped in exquisite 3-D detail the binding of the ZMapp antibodies to the Ebola virus.

Ward lab, Scripps Research Institute

In the image above, the surface of one part of the Ebola virus appears as a white disc, while the white tree-like appendage depicts the spike protein that enables the virus to fuse with human cells and insert its genetic material.

The researchers discovered that two of the antibodies in ZMapp (indicated by red and yellow) disrupt the fusion process, neutralizing the virus and preventing it from attaching to the cell. Because these two antibodies do roughly the same thing, the researchers speculated that it might be possible to eliminate one from the ZMapp cocktail, which may make the drug less expensive and easier to manufacture. Meanwhile, ZMapp’s third antibody (blue) serves as a beacon for the immune system. Although this antibody can’t neutralize the virus, it binds to the spike protein and alerts the immune system that the virus has invaded the body and must be destroyed.

Andrew Ward, one of the leaders of the NIH-supported Scripps team, says the findings provide a clearer scientific rationale for why ZMapp might be effective in combating the virus. Of course, future clinical studies will be needed to determine whether that’s indeed the case. But we’re clearly off to a solid start.

So far, Ward and his colleagues at Scripps have collaborated with colleagues at Mapp Biopharmaceutical to image more than 20 antibodies to determine whether it might be possible to develop a more effective cocktail than ZMapp. The Scripps team is also planning to image antibodies in the bloodstreams of people who’ve survived Ebola without taking ZMapp or other drugs, to learn more about how their immune systems defeated the virus.

From a broader perspective, the findings suggest that the Ebola virus has at least two exploitable points of structural vulnerability. These viral “soft spots” will help to inform future efforts at drug and vaccine development. For example, vaccine researchers might want to target the spike protein to block the fusion process, while researchers trying to come up with new therapies might follow the lead of the blue antibody and look for molecules that alert the immune system to destroy infected cells.

Scientists also can use these soft spots to track the evolution of the Ebola virus, something that I wrote about in an earlier post. Because the Ebola virus mutates constantly, we need to make sure that the proteins targeted by ZMapp and other potential therapies and vaccines haven’t mutated, rendering the treatment and prevention strategies less than effective.

Whether on the basis of history, archaeology, philosophy, theology, or genomics, we humans are all one family. So when one part of the family is afflicted, we all are. Whether disease is happening in West Africa or West L.A., we at NIH will work tirelessly to develop the means to prevent and treat it. The president’s visit provided a wonderful encouragement to all who labor here.

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Creative Minds: Tackling Chemotherapy Resistance

Dr. Francis Collins, National Institutes of Health — Tue, 28 Oct 2014 16:00:00 -0400

For many young scientists, nothing can equal the chance to have a lab of one’s own. Still, it often takes considerable time to get there. To help creative minds cut to the chase sooner, the NIH Director’s Early Independence Awards this year will enable 17 outstanding young researchers to skip post-doctoral training and begin running their own labs immediately.

Today, I’d like to tell you about one of these creative minds. His name is Aaron Meyer, a cell signaling expert at the Massachusetts Institute of Technology in Cambridge, and his research project will take aim at one the biggest challenges in cancer treatment: chemotherapy resistance.

Specifically, Meyer’s work focuses on a group of proteins, called receptor tyrosine kinases (RTKs), which are embedded in the outer surface of just about every cell in our body. RTKs bind various hormones and growth factors that activate internal signaling networks critical for cell communication, growth, and movement. RTKs are so fundamental to the core functions of our cells that many cancers hijack them to fuel their growth and resist certain chemotherapy drugs.

For example, breast cancers that produce too much of an RTK, called human epidermal growth factor receptor 2 (HER2), tend to grow faster and respond poorly to standard chemotherapy. Blocking the receptor with drugs (most famously Herceptin®) helps to stop the growth of the HER2-positive breast cancers. But it doesn’t always work, and that has puzzled and frustrated patients and oncologists for many years. Recent studies suggest that when a drug blocks a particular RTK from signaling, other nearby clusters of RTKs may step in and take their place. Such redundancy might explain the resistance of cancer cells to drugs that otherwise should kill them.

Meyer wants to conduct a series of systematic experiments aimed at investigating how such resistance occurs. First, he will seek to identify which set(s) of proteins inside the cell interact with each RTK to mute or amplify its particular signal and under what circumstances those modulations occur. He also wants to explore how these RTK-protein interactions mesh with larger signaling networks inside the cell. By modeling all of these interactions, it may be possible to discover better targets for future cancer therapies.

This research agenda may sound very ambitious, but complexity has never daunted Meyer. As a child, he liked to take apart television sets, computers, calculators, and any other electronic gadget to see what made them tick. Not only was this kid into deconstructing devices (much to the dismay of his parents), he went on to build entirely new gizmos from their parts! Meyer seemed destined to become an electrical engineer until high school biology teachers impressed upon him that the human body is a profoundly complicated machine. Unlike engineering, where he assembled man-made parts into functioning devices, cells and living organisms remained poorly understood, featuring yet-to-be-discovered protein parts and interactions. Combining his interests in engineering and biology as an undergraduate student at the University of California, Los Angeles, Meyer chose to pursue a career in bioengineering.

Armed with an Early Independence Award and a freshly minted Ph.D., earned in the labs of MIT’s Douglas Lauffenburger and Frank Gertler, Meyer is now busy setting up his own lab and recruiting talented graduate students and postdocs to help realize his research vision. For the sake of all those awaiting more effective cancer therapies, let’s hope this young creative mind meets with success.

(Image via sfam_photo/Shutterstock.com)

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Cool Videos: Rapping for Research

Dr. Francis Collins, National Institutes of Health — Thu, 09 Oct 2014 09:00:00 -0400

Many entries in the NIH Common Fund video competition highlight particular research projects. But in the original rap video that I’m featuring today, a group of New York researchers deliver a message about the central importance of collaboration for moving scientific breakthroughs from the bench to the bedside.

Or, as the researchers themselves put it, “This video describes, in rap, the Weill Cornell Clinical and Translational Science Center, a partnership of world-class academic institutions and health centers in New York City. The CTSC supports the translation of basic science research into better patient care that will improve our nation’s health. It fosters high-risk/high-reward research, enabling the development of transformative tools and methodologies, and filling fundamental knowledge gaps. The CTSC seeks to change academic culture to foster collaboration and was made possible by a Clinical and Translational Science Award from the NIH Common Fund, administered by the National Center for Advancing Translational Sciences.”

Links:

Weill Cornell Clinical and Translational Science Center

Clinical and Translational Science Awards (NCATS)

NIH Common Fund Video Competition

NIH support: Common Fund; National Center for Advancing Translational Sciences

( Image via Monika Wisniewska / Shutterstock.com )

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Imagine If Thousands of Medical Researchers Could Have a Quick Conversation

Dr. Francis Collins, National Institutes of Health — Fri, 08 Aug 2014 09:00:00 -0400

Today’s scientists find it tough to keep up with all of the latest journal articles, innovative methods, and interesting projects of colleagues in their fields. That’s understandable, because there are tens of thousands of journals, hundreds of conferences in major fields, dozens of emerging technologies, and huge geographic distances separating researchers who may share common interests. But science is increasingly a team sport—and it’s important to provide scientists with as many avenues as possible through which to interact, including commenting on each other’s work.

To encourage such exchanges, NIH’s National Center for Biotechnology Information recently developed PubMed Commons , a resource that gives researchers the opportunity to engage in online discussions about scientific publications 24/7. Specifically, this service allows scientists with at least one publication to comment on any paper in PubMed—the world’s largest searchable database of biomedical literature, with more than 3 million full-text articles and 24 million citations.

There are a lot of reasons to participate. Authors of biomedical research papers can update and receive feedback on their papers from fellow scientists around the globe. Comments can guide further research by identifying and sharing links to other relevant papers, linking to datasets, replication efforts, or blogs. Researchers can also link to articles in non-biomedical journals that might otherwise be overlooked.

Since the service was launched a few months ago, 5,000 scientists (who have at least one publication in PubMed) have joined PubMed Commons—posting about 1,600 comments. The quality of these comments has been good, thanks in part to a member-based rating system that flags the comments found to be most useful.

But numbers don’t tell the whole story—what are real-life researchers actually talking about on PubMed Commons? Here are just a few examples to give you an idea of the types of discussions that are taking place around this virtual water cooler. One researcher posted highlights from an online journal club discussion of a randomized controlled trial, and then added a link to a YouTube interview with the principal investigator of the study. Another posted a link to her freely accessible data sets. There also was an instance in which a scientist raised concerns about a cross-contaminated cell line that was used in a study and began a conversation with researchers about where to find lists of other problematic cell lines.

In short, PubMed Commons is a great tool to bring scientists together to share resources and knowledge, boost collaboration, and enhance our efforts to advance biomedical knowledge—with the ultimate goal of improving human health. So, I encourage every researcher with one or more articles in PubMed to take the time to join PubMed Commons (by following these instructions ) and then become an active, thoughtful part of these important conversations.

( Image via Dragon Images / Shutterstock.com )

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NIH’s Formula for Innovation: People + Ideas + Time

Dr. Francis Collins and Sally Rockey, National Institutes of Health — Thu, 24 Jul 2014 09:00:00 -0400

In these times of tight budgets and rapidly evolving science, we must consider new ways to invest biomedical research dollars to achieve maximum impact—to turn scientific discoveries into better health as swiftly as possible. We do this by thinking strategically about the areas of research that we support, as well as the process by which we fund that research.

Historically, most grants funded by the National Institutes of Health have been “project-based,” which means that their applications have clearly delineated aims for what will be accomplished during a defined project period. These research project grants typically last three to five years and vary in award amount. For example, the average annual direct cost of the R01 grant—the gold standard of NIH funding—was around $282,000 in fiscal 2013, with an average duration of 4.3 years.

We often hear from investigators at all career stages that they spend a significant portion of their careers writing grant applications, consuming precious time that could otherwise be spent conducting research. This grant-writing treadmill is fueled by several factors: fierce competition for limited research dollars, made worse by the current funding situation, which has caused success rates to fall to historic lows; the need to support multiple research projects in a productive laboratory; and desires to pursue new research directions when opportunities arise.

To meet the changing needs of the biomedical workforce, NIH is piloting the concept of awarding longer grants that provide more stable support for investigators at all career stages. It is our hope that with more sustained support, investigators will have more freedom to innovate and explore new lines of inquiry. The NIH Pioneer Award, supported by the Common Fund, represents a compelling example of such an approach. Pioneer Awards support individual scientists of exceptional creativity, who propose pioneering—and possibly transformative approaches—to major research challenges. This award allows for $500,000 annually in direct costs for five years, and in a recent evaluation was shown to facilitate a high level of innovation and productivity.

Moving forward, several NIH institutes and centers will be developing new funding opportunities to offer more sustained support to investigators’ research programs. These longer term awards will not follow a one-size-fits-all approach; leaders of each NIH IC will decide if they wish to embark on these awards based on the balance of their portfolios and their strategic planning needs. In addition, each IC will decide the appropriate size and duration of their awards. While applications for these awards will not require specific aims in the traditional R01 format, investigators will describe their research plans and will demonstrate how they will leverage and translate their prior accomplishments into approaches that will shape their future research.

First out of the chute is the National Cancer Institute’s Outstanding Investigator Award, which will provide long-term support to investigators who have extraordinary records of cancer research productivity and who propose to conduct exceptional research. Applicants may request up to $600,000 annually in direct costs, for up to seven years. The National Institute of General Medical Sciences (NIGMS) recently issued a request for information to obtain community feedback on their concept of the “Maximizing Investigators’ Research Award.” This award would support all NIGMS-funded research in an investigator’s laboratory. Funding would range from $150,000 to $750,000 in direct costs annually for five years (the current average for an NIGMS R01 is about four years). Other NIH institutes and centers will likely follow soon with their own funding opportunities.

NIH is not alone in employing models of sustained support. For many years, the Howard Hughes Medical Institute has promoted the philosophy of supporting “people, not projects.” The HHMI Investigator Program provides five years of renewable support to individuals who have the potential to make significant contributions to science. The Canadian Institutes of Health Research is in the midst of piloting its Foundation Scheme, which supports a broad base of researchers across career stages, areas and disciplines. CIHR Foundation Scheme grants vary depending on the research field and scope of research activities. Established investigators are awarded seven-year grants, while new/early career investigators receive five-year grants. Other organizations using similar approaches include the Medical Research Council Programme Grant, the Wellcome Trust Investigator Award and the MacArthur Fellows Program.

Because NIH’s overall budget is not affected by the introduction of this new type of award, the research community might ask whether these awards will come at the expense of other programs. Very mindful of this concern, each NIH institute and center will carefully consider its budget as it decides whether to use this funding approach. We expect that some may issue a small number of awards at first, as they dip their toes in the water.

It is important to note that these awards will support talented people from a range of career stages, backgrounds, and disciplines. These new awards will complement other NIH funding opportunities that give applicants more flexibility in their research approaches. For example, the National Institute of Mental Health Biobehavioral Research Awards for Innovative New Scientists support the research and career development of outstanding scientists who are in the early, formative stages of their careers and who plan to make a long-term commitment to research in NIMH’s specific mission areas. The National Institute of Environmental Health Sciences Outstanding New Environmental Scientist Award helps talented early-stage investigators launch innovative research programs focused on the understanding of environmental exposure effects on people’s health.

When discussing research funding paradigms, it’s often said that one supports either people or projects. But these are not mutually exclusive concepts. NIH has always supported researchers and their ideas for advancing scientific discovery and improving public health. Ultimately, we need to know what’s the right balance of different types of awards in the NIH portfolio. To answer that question, NIH plans to evaluate these new sustained award programs and closely monitor their effects on the scientific community.

Biomedical research is a complex enterprise that is constantly evolving. So, for the good of biomedical research and all of the people NIH is trying to help, the agency must always be on the lookout for new ways of fostering the vibrancy of this enterprise. It’s time to move forward with this new formula for innovation, keeping in mind these words from Winston Churchill: To improve is to change.

Francis Collins is director of the National Institutes of Health, and Sally Rockey, Ph.D., is deputy director for Extramural Research.

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At NIH, Biomedical Research Is Enough to Make You Break Into Song

Dr. Francis Collins, National Institutes of Health — Mon, 07 Jul 2014 15:59:42 -0400

Happy 10^th anniversary to the National Institutes of Health’s Common Fund! It’s hard to believe that it’s been a decade since I joined then-NIH Director Elias Zerhouni at the National Press Club to launch this trans-NIH effort to catalyze innovation and speed progress across many fields of biomedical research.

Allow me to take this opportunity to share just a bit of the history and a few of the many achievements of this bold new approach to the support of science.

Let’s start with the history. In 2003, Dr. Zerhouni, who served as NIH director from 2002 to 2008, and the leaders of NIH’s 27 institutes and centers (I was the Director of the National Human Genome Research Institute at the time) sat down to develop a plan we dubbed the NIH Roadmap. This plan outlined a series of ambitious goals aimed at encouraging the development of innovative technologies and research tools, with the potential to produce revolutionary advances in many fields of biomedical science. These were multidisciplinary goals that would benefit many different kinds of research, but couldn’t readily fit into the plans of any single institute or center.

To support this vision, NIH needed to create a new funding mechanism that transcended existing organizational boundaries. So, we decided that each year every institute and center would contribute 1 percent of its annual budget to a designated fund within the NIH Office of the Director. In 2006, when Congress provided language to establish this fund as an official line item in the NIH budget, the name NIH Roadmap gave way to the NIH Common Fund.

Since I started this blog a couple of years ago, I’ve featured a lot of transformative research that has been the focus of Common Fund efforts, including the Human Microbiome Project, Big Data to Knowledge, Extracellular RNA, Nanomedicine, Epigenomics, Undiagnosed Diseases Program, and High-Risk, High-Reward Research. Some of these advances have already transformed the way we do science and expanded our understanding of human health and disease—and others are sure to do so in the future.

Consider the impact of just one of these projects: the Human Microbiome Project, which aimed to characterize the microbes inhabiting the human body—including nasal passages, oral cavities, skin, gastrointestinal tract and urogenital tract. The first phase of this project gave us a census of many of the microbes living in and on us, revolutionizing the way we view ourselves. No longer can we think of ourselves as isolated organisms. Rather, each one of us is an ecosystem teeming with microbes that influence our health status in ways we’re only beginning to appreciate.

In addition to funding collaborative projects that involve hundreds of scientists supported by several institutes, we also use the Common Fund to support the High-Risk, High-Reward Program, which funds individual scientists with particularly innovative ideas or transformative technologies that, because of their novelty, may lack the preliminary data typically used to evaluate NIH grant proposals. For example, two such researchers, Karl Deisseroth of Stanford University and Edward Boyden of MIT, received the NIH Director’s Pioneer and New Innovator awards respectively to develop a method for controlling the activity of neurons with light. Their high-risk projects launched the field of optogenetics, which has revolutionized the study of neuroscience. I’ve profiled many of the 2013 HRHR awardees in my Creative Minds series of blog posts. Along with winners from past years, this represents an absolutely amazing group of scientists. Who knows how many new fields they will launch?

To celebrate the past decade of discovery, we recently hosted the Common Fund Symposium today. The symposium featured talks by Dr. Zerhouni, now President of Global R&D at Sanofi, as well as many of the remarkable scientists who have led the large multidisciplinary projects or who have received HRHR awards.

Over the course of the day, we revealed the winners of the first-ever Common Fund video competition, in which researchers describe their work to the public in some wonderfully creative (and sometimes humorous) ways. If you only have time to watch one of these productions, let me recommend this one on Alzheimer’s disease research that’s being honored as the “NIH Select” video.

Finally, if you watch the videocast to the end of the symposium, you might even catch me singing a song written by a Common Fund researcher for the song contest and dedicated to all who have made—and will continue to make—this endeavor such a resounding success for biomedical science.

Onward!

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