With Wuhan virus genetic code in hand, scientists begin work on a vaccine

When a newly organized vaccine research group at the U.S. National Institutes of Health (NIH) met for the first time this week, its members had expected to be able to ease into their work. But their mandate is to conduct human trials for emerging health threats – and their first assignment came at shocking speed.
In just three months time, they likely will be testing the first of a number of potential experimental vaccines against the new SARS-like coronavirus that is spreading in China and beyond.
“I told them, ‘you are going to have your baptism of fire, folks’,” Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases within NIH, said of his inaugural address to the group this week.
Three months from gene sequence to initial human testing would be the fastest the agency has ever gotten such a vaccine off the ground, Fauci said.
The outbreak, which began in the central Chinese city of Wuhan in December, as of Friday had infected more than 800 people in China and killed 26. Cases have also been confirmed in Thailand, Vietnam, Singapore, Japan, South Korea, Taiwan, Nepal and the United States.
Chinese scientists were able to quickly identify the genetic sequence of the new coronavirus and officials posted it publicly within a few days, allowing scientific research teams to get to work right away.

With the genetic code in hand, scientists can start vaccine development work without needing a sample of the virus.
During the deadly 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, it took U.S. scientists 20 months to go from genetic sequence to the first phase of human trials. By that time, the outbreak was under control.
This time, research groups worldwide are already executing plans to test vaccines, treatments and other countermeasures to stop the newly identified virus from spreading globally.
MULTI-PRONGED APPROACH
They are attacking from several angles, with global health and epidemic response agencies hoping at least one treatment will be in human trials within a few months.
Fauci’s agency is partnering with U.S. biotech Moderna Inc, which specializes in vaccines based on ribonucleic acid (RNA) – a chemical messenger that contains instructions for making proteins.
That team hopes to make an RNA vaccine based on one of the crown-like spikes on the surface of the coronavirus that gives the family of viruses their name, an approach that, unlike many vaccines, would not expose people to the virus.
At the University of Queensland in Australia, scientists backed by the global health emergency group the Coalition for Epidemic Preparedness Innovations (CEPI) said they are working on what they describe as a “molecular clamp” vaccine approach.
The technology adds a gene to viral proteins to stabilize them and trick the body into thinking it is seeing a live virus and create antibodies against it.
Keith Chappell, an expert in the University’s school of chemistry and molecular biosciences, said the technology is designed as “a platform approach to generate vaccines against a range of human and animal viruses.”
It has already shown promising results in lab tests on other dangerous viruses such as Ebola and the coronavirus that causes Middle East Respiratory Syndrome (MERS)- a cousin of SARS and the Wuhan virus.
Novavax, which already has a vaccine in development against MERS, says it is now working on one for the Wuhan coronavirus.
Scientists also are turning to infection-fighting proteins known as monoclonal antibodies, or mAbs, that were developed against the SARS and MERS coronaviruses.

The hope is that similarities with the Wuhan virus will offer enough overlap in the antibodies to help people infected in the China outbreak.
Vir Biotechnology Chief Scientific Officer Herbert Virgin said his company has a library of monoclonal antibodies that have shown some success against SARS and MERS in lab tests.
Some of these antibodies have been shown to neutralize coronaviruses, Virgin said, and “may have the potential to treat and prevent (the) Wuhan coronavirus.”
https://www.reuters.com/article/us-china-health-vaccines/with-wuhan-virus-genetic-code-in-hand-scientists-begin-work-on-a-vaccine-idUSKBN1ZN2J8

‘Single Biggest Contributor’ to Medical and Mental Illness

Stephen M. Strakowski, MD: Hello. I’m Dr Stephen M. Strakowski, acting senior associate dean for research at the Dell Medical School at the University of Texas at Austin. I’m speaking today with two of my expert colleagues here. Dr Elizabeth Lippard is an assistant professor in our department and has been here the longest of anybody else other than me. Dr Charles Nemeroff joined us about a year ago and is now acting as chair in the department of psychiatry, in addition to creating and directing the Institute for Early Life Adversity Research.
We’re speaking with Drs Lippard and Nemeroff about a seminal paper they just published in the American Journal of Psychiatry, reviewing the impact of early life adversity on people, their lives, their medical history, and potentially what goes on in the brain. I want to talk with them today about how all of us who practice mental health care might apply their important work.
To begin, can you tell us about the field of early life adversity and how common such experiences are in patients?
Charles B. Nemeroff, MD, PhD: The entire field was really launched by the phenomenal Adverse Childhood Experiences (ACE) Study, which was funded by the Centers for Disease Control and Prevention (CDC). Investigators went to Kaiser Permanente in San Diego and sampled 17,000-plus individuals.
The results were just astounding. In this nonclinical general population, the rates of child abuse in the form of physical abuse, sexual abuse, emotional abuse, and neglect were remarkably high, ranging—depending on the category—from about 8% to 25%. These results have since been confirmed in several subsequent studies from the CDC and others. This is really a public health tragedy.
Strakowski: It sounds like an epidemic. If we imagined a new virus suddenly affecting 1 in 4 kids, I assume that people would be quite upset and doing something about it.
Nemeroff: This is the single biggest contributor to the risk for psychiatric and medical disorders, more than any single gene or factor. It increases the risk for heart disease, stroke, depression, drug abuse, suicide. It’s awful.

Strakowski: How should people be thinking about the potential impact of these risks?
Elizabeth Lippard, PhD: Piggybacking on what Charlie was saying, if you look at the prevalence of childhood maltreatment, early life stress, and mood disorders, you see rates as high as 50%-60%. If you look at individuals with mood disorders and comorbid addiction, rates are even higher.
We consistently see across studies that it’s associated not only with increased risk for onset, but also increased risk for disease recurrence. In terms of mood disorders, this means more mood symptoms occurring over time with greater severity. You also see a relationship in terms of more complicated clinical cases: more comorbidities, with addiction and medical morbidities as well.

Considering the clinical impact that it’s having on disease outcomes, and how prevalent child maltreatment is, this is a large percentage of disease burden that can be directly contributed to early life stress. It points to a very powerful target that we need to be thinking about when treating disease.
Strakowski: I think when a lot of us consider these kinds of abusive histories, we tend to then jump to post-traumatic stress disorder (PTSD) as the only consequence that we need to contemplate. But you’re saying that it’s much broader than that.
Lippard: Yes, definitely. Whenever you think about childhood maltreatment, it really crosses diagnostic boundaries. It increases the risk for mood disorders, addiction, PTSD, schizophrenia, etc., and you see it across the board.

The Physical Tolls of Early Trauma

Nemeroff: If you look at victims of child abuse and neglect when they are adults with psychiatric disorders, they are much more treatment resistant than patients with comparable disease severity without this history. We believe that the reason for that is that early life trauma results in brain and body changes that persist for the lifetime of the individual. These folks have a different biology, a different brain, and their treatment response for bipolar disorder, for depression, for PTSD is just terribly worse than it is for people without this history.

Strakowski: You perfectly anticipated my next question. Do we have some idea of what early life trauma is doing to the person’s brain or body that is setting them up for these consequences?
Lippard: We do. There’s a wealth of research out there pointing toward long-lasting neurobiological and immune mechanisms, as well as the hypothalamic pituitary adrenal stress response system, and changes within these systems that may be contributing to these outcomes.
In terms of the brain, we see long-lasting changes in structure and function within systems that regulate stress response and emotional, higher-order cognitive processes. It really is giving us an insight into the brain systems that may be so critical for developing psychopathology over time following childhood maltreatment.

One of the things that’s really striking to me when you look at the literature is the more recent emergence of longitudinal studies, which suggest that changes in the brain really can predict future mood symptoms, recurrence, and severity. Traditionally, we started with a wealth of cross-sectional studies in this area, but now these longitudinal studies coming out have given us a lot of power to hone in on certain systems of the brain that can hopefully be targeted for intervention.

Ask Patients About Their Childhoods, Regardless of Your Specialty

Strakowski: Clinicians and providers across many different specialties will be watching this. This applies to patients with psychiatric conditions but, as you implied, medical conditions as well. How do you recommend they ask their patients about this?
Nemeroff: First, for the clinicians out there, it’s extremely important that you get this information from the patient. You need to know it.
There are several screening tools available to help you obtain this information. There’s the ACE questionnaire, although I’m not particularly fond of it. I think the Childhood Trauma Questionnaire is somewhat better. There are others as well. These are self-rating scales, so they won’t take any of your time. We have every patient fill out the scales, which gives you a good indication of their history, as patients will often put things down on paper that they don’t want to tell you.
Second, it often takes several visits with a patient before they’re comfortable enough to talk about their trauma. I’ve seen many patients with treatment-resistant depression who finally revealed to me that they had suffered a childhood rape or some other awful experience. If you’re seeing a treatment-resistant patient, you should be thinking about child abuse and neglect.
Strakowski: In anticipating my talk with you both today, I gave some thought to my own clinical practice. On a given day in my clinic, I bet 80% of the young people I treat have these histories. It’s hard to overexaggerate the risk.

An Epidemic Without a Solution

Strakowski: From a treatment perspective, do you consider maybe doing something differently if you are aware that a patient has this history?
Nemeroff: We know that in every study that we looked at, when you parse out the patients with early life trauma and compare them to those who don’t have that history, they have a poorer outcome. But part of the problem is that there are no treatment trials that have specifically asked this question. In terms of designing a treatment, my gut feeling, which is not science, is that they would do better with a combination of pharmacotherapy and psychotherapy.

One of my concerns is that, as pharmaceutical companies come to realize that these patients actually have poor treatment outcomes, they’re starting to eliminate them from clinical trials.
Strakowski: Which is the exact opposite of what we wish would happen.
Nemeroff: It’s sort of like what’s happened with pregnancy; we don’t know how to treat pregnant women because they’re never allowed in trials.

Strakowski: To me, it sounds like we have an epidemic for which we’re not aggressively trying to find a solution. Does it feel like the psychiatric or psychological professional associations and organizations are making this issue sufficiently visible to engender some response?
Nemeroff: I think that a number of the organizations you’re referring to have done their best, but it’s not enough. First, from a medical education point of view, there is very little training about child abuse and neglect in the curriculum.
Strakowski: I probably received none, roughly 200 years ago when I was in training, and I’m guessing the same is true for you.

Nemeroff: Absolutely. There’s very little attention paid to this. Of all of the physicians, I think pediatricians have been the most sensitive to this. But as Beth alluded to, this a population with an increased risk for diabetes, certain forms of cancer, heart disease, and stroke, and specialists in those areas don’t ask about child abuse and neglect.
Strakowski: There’s a lot more detail to this very important topic in the paper, authored by Drs Lippard and Nemeroff, which is titled “The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders.” I hope you all will take a look at that, and I hope you found our conversation interesting. Thank you all for listening today.
Stephen Strakowski, MD, is the founding chair and professor of psychiatry at Dell Medical School, University of Texas. His research focuses on the brain changes that occur at the onset of bipolar disorder.
https://www.medscape.com/viewarticle/923389#vp_1

Weight Training Plus Aerobics Is Best to Ward Off Obesity

Participation in either strength training or aerobic exercise is associated with a lower prevalence of obesity, but combining both is the most effective way to reduce the likelihood of becoming obese, researchers say.
In a large survey of roughly 1.7 million US adults, those who met both aerobic and muscle-strengthening exercise guidelines — which call for ≥ 150 minutes of moderate aerobic exercise and at least two muscle-strengthening exercises per week — had a lower prevalence of obesity than those who did not.
Of interest, the survey also showed that the greater the level of obesity, the larger the benefit that was derived from combining both modalities, said lead author Jason A. Bennie, PhD, of the University of Southern Queensland Physically Active Lifestyles (USQ PALs) research group, Australia. The findings were published online in Obesity.
“I am a behavioral physical activity epidemiologist and my area of interest is in physical activity and chronic disease,” Bennie told Medscape Medical News.
“Both aerobic and muscle-strengthening exercise are recommended for obesity prevention, but it is not known which modality is most effective at the population level,” he explained.
“Most of the evidence around health is based on aerobic exercise like walking, cycling, and jogging. But in this particular study, I was interested in looking at the association between different combinations of strength training and aerobic exercise and how they affected weight,” he said.
In an accompanying editorial, Timothy S. Church, MD, PhD, Pennington Biomedical Research Center, Baton Rouge, Louisiana, notes: “This is by far the largest study to ever examine the combination of aerobic and strength training, and it provides further evidence for the value of combining the two exercise modalities.”

“Epidemiologists Like Big Data”

Bennie and colleagues say the independent and/or combined associations of moderate to vigorous physical activity (aerobic exercise) and muscle-strengthening exercise with obesity at the population level are largely unknown.
“To our knowledge, this is the first population-level study examining the associations between muscle-strengthening exercise, combined moderate to vigorous physical activity and muscle-strengthening exercise, and obesity,” they write.
Bennie and his team pooled data on 1,677,108 adults age 18 years and older from four US Behavioral Risk Factor Surveillance System (BRFSS) surveys for 2011, 2013, 2015, and 2017.
“This is a big survey which is run every year in the United States, but every second year they include a physical activity component. I pulled all the data on people’s physical activity and how this was associated with their body mass index (BMI). The reason why we chose US data is because the United States has a good surveillance system to monitor their population,” Bennie said.
And “epidemiologists like big data,” he observed.
Just over one fourth of respondents were ≥ 65 years, 51.6% were female, and most were white or Hispanic.
Over half had never smoked, and 18.6% reported “excellent” health.
To determine exercise habits, physical activities were coded as “aerobic” or “nonaerobic” using a list of 56 activities, with examples of aerobic activities including walking, jogging, tennis, and soccer. To assess strength training, participants were asked: “Do not count aerobic activities like walking, running, or bicycling. Count activities using your own body weight like yoga, sit-ups, or push-ups, and those using weight machines, free weights, or elastic bands.”
Forty percent of respondents reported they did not meet guidelines for aerobic or strength-training exercise, 9.5% met strength-training guidelines only, 30.2% met aerobic guidelines only, and 20.2% met guidelines for both.
Overall, 35.6% had a BMI of 18.5-24.9 kg/m² (healthy weight), and 28.9% had a BMI of ≥ 30 kg/m² (obese).
Obese respondents were further categorized into the following three classes:

• Class I obesity and above (BMI ≥ 30.0 kg/m² but < 35.0 kg/m²)
• Class II obesity and above (BMI ≥ 35.0 kg/m²  but < 40.0 kg/m²)
• Class III obesity and above (BMI ≥ 40.0 kg/m²)

Associations Were More Pronounced for Higher Obesity Classes

Analysis of the data showed that respondents who met both exercise guidelines had the lowest adjusted prevalence ratios (APRs) for obesity across all classes of obesity compared with those in the other exercise categories. Their APRs ranged from 0.27 to 0.50.
Interestingly, noted Bennie, the prevalence ratios (PRs) were lowest for all physical activity categories for those with Class III obesity.
Adjusted Prevalence Ratios (APRs) for Meeting Both Exercise Guidelines

Obesity Class	APR	95% CI
Class I obesity and above (BMI ≥ 30.0 kg/m2)	0.54	0.53 – 0.54
Class II obesity and above (BMI ≥ 35.0 kg/m2)	0.32	0.31 – 0.33
Class III obesity and above (BMI ≥ 40.0 kg/m2)	0.21	0.20 – 0.21

The associations remained after adjusting for gender, socioeconomic status, education, lifestyle characteristics, and chronic health conditions, Bennie said.
“The bottom line is that it is the combination of both weight training and aerobics that is the most effective for reducing the likelihood of obesity,” he stressed.
“The real problem is that once you get into the higher levels of obesity, it is very difficult to go back into normal weight. It’s a very slippery slope. We need to help stop people from getting into those higher levels of obesity, when things really start going awry with their metabolism, their blood glucose, their depression,” he emphasized.
“While prospective studies and controlled designs are needed to better support causal evidence, this study suggests that a combination of moderate to vigorous physical activity and muscle-strengthening exercise has the most beneficial associations with overall obesity and obesity severity,” Bennie and colleagues reiterate.

Emphasize Importance of Combining Aerobic and Strength Training

In his editorial, Church notes that “while cross-sectional designs do not allow for cause-and-effect determination, this manuscript is still a valuable contribution to the literature.”
He emphasizes that BMI does not differentiate fat mass from lean muscle mass, and the fact that strength training promotes muscle mass creates the opportunity for misclassification, “yet the weight training was still found to be associated with a lower risk of obesity as defined by BMI.”
“In my experience, few individuals are aware of the strength training recommendations. This is unfortunate, as the evidence is clear that while strength training has health benefits, aerobic training has more; however, doing both is optimal,” he adds.
This study “provides further evidence of the need for emphasis on the importance of including strength training in one’s physical activity program.”
“For those individuals focused on preventive measures to promote healthy aging, the importance of combining aerobic and strength training exercise needs to be emphasized,” he concludes.
Bennie and Church have reported no relevant financial relationships.
Obesity 2020;28:224,371-378. Full text, Editorial
https://www.medscape.com/viewarticle/924131#vp_1

Human and Analogue Insulins Equivalent for Major Outcomes

There was no difference between human and analogue insulin in terms of cardiovascular and mortality outcomes, but cost is another matter, said authors of a large retrospective study.
With data on 127,000 adults with type 2 diabetes who initiated insulin during 2000-2013 and median 2.5 years of follow-up, users of human versus analogue insulin products had similar rates of major cardiovascular events, cardiovascular mortality, and overall mortality, reported Patrick O’Connor, MD, of the HealthPartners Institute in Minneapolis, and colleagues.

More specifically, as they outlined in JAMA Network Open, the study’s five main outcomes had the following adjusted hazard ratios for human versus analogue insulin:

• Overall mortality: HR 1.15 (95% CI 0.97-1.34)

• Cardiovascular mortality: HR 1.26 (95% CI 0.86-1.66)

• Myocardial infarction: HR 1.11 (95% CI 0.77-1.45)

• Cerebrovascular accident: HR 1.30 (95% CI 0.81-1.78)

• Congestive heart failure hospitalization: HR 0.93 (95% CI 0.75-1.11)

“Our results suggest that cardiovascular outcomes and mortality should not be a motivating factor in the decision to start human vs analogue insulin therapy in insulin-naive adults with type 2 diabetes,” the researchers wrote. “Other relevant factors to consider include hypoglycemia, glycemic control, cost, and ease of use. Recent reports have shown similar effects of human and analogue insulins on control of glucose levels and serious hypoglycemic events in primary care practice, which suggest that human and analogue insulins are safe and effective treatments in type 2 diabetes.”
Most insulin users in the U.S. — approximately 90% — use analogue insulins, which were first introduced in 1996. They became widely used despite higher costs, in part because studies indicated lower rates of mild hypoglycemia.
O’Connor and co-authors added that while hypoglycemia rates have been well studied, the effects of human versus analogue insulin on cardiovascular events and mortality have not. Both types of insulin were introduced before 2008 when the FDA mandated cardiovascular outcomes trials for diabetes drugs. Some major clinical trials, such as the Diabetes Control and Complications Trial and the U.K. Prospective Diabetes Study, did not include analogue insulins.
A 10-mL vial of human insulin lists for approximately $25, compared with more than $280 for analogue insulin, O’Connor’s team noted. “The price differential between human and analogue insulins and the lack of significant differences in rates of serious hypoglycemia in recent reports have sparked new interest in the use of human insulin as a way to make health care more affordable to patients with diabetes.”

Previous research on this topic, however, reported mixed results. Those studies also had significant limitations in terms of participant selection, sample size, and analytic details. The current study improved on that research by including a large number of U.S. participants who received care in community-based clinics, by having relatively complete clinical outcome data, and by using machine learning and other advanced statistical methods to analyze the data, O’Connor and co-authors explained.
The 127,600 study participants were treated in four different healthcare systems: HealthPartners in Minnesota, Kaiser Permanente Colorado, Kaiser Permanente Northern California, and Kaiser Permanente Southern California. The mean age of participants was 59, and approximately half were men.
Most participants (85%) used human insulin. Two exposure groups defined by continuous treatment with the same insulin therapy, either human or analogue, were compared. The investigators analyzed medical records for outcomes, controlling for factors that included patient demographics, comorbidities, concomitant medications, and smoking.
Robert Eckel, MD, of the University of Colorado Anschutz Medical Campus in Aurora, who was not involved in the research, said the large number of human insulin users was unusual. Still, “with all of the limitations of retrospective analysis of medical records, the results are not surprising,” he told MedPage Today via email. “However, the discrepancy between clinics in insulin use is of note with three of four locations using mostly human insulin. Moreover, the ongoing use of human insulins 10-15 years after analogue insulins were FDA approved is unexpected based on U.S. data in 2010, and despite the escalating cost of analogues.”
A chief limitation of the study, O’Connor and colleagues said, was its retrospective design. “However, owing to the high cost of conducting large randomized trials in a rapidly evolving insulin market, there is little chance that a large randomized trial will address cardiovascular outcomes of human vs other insulins, although manufacturers have compared newer and older analogue insulins,” the team wrote. “Results show few differences in cardiovascular events, suggesting that newer analogue insulins are unlikely to have better cardiovascular outcomes than the analogue insulins we evaluated.”

The study was supported by the National Institutes of Health (NIH).
O’Connor reported grants from the NIH and the Patient-Centered Outcomes Research Institute; one co-author reported a relationship with a pharmaceutical company (Merck) outside of the study.

• Primary Source

  JAMA Network Open

  Source Reference: Neugebauer R, et al “Comparison of mortality and major cardiovascular events among adults with type 2 diabetes using human vs analog insulins” JAMA Network Open 2020; 3(1): e1918554.

https://www.medpagetoday.com/cardiology/diabetes/84521

China built Wuhan lab to study SARS, Ebola; experts warned of virus ‘escape’

• The Wuhan National Biosafety Laboratory is the only lab in China designated for studying dangerous pathogens like SARS and Ebola
• Ahead of its January 2018 opening, biosafety experts and scientists from the US expressed concerns that a virus could escape the lab
• In 2004, a SARS virus ‘leaked’ from a lab in Beijing 
• Experts say the coronavirus that’s infected more than 800 people mutated in animals and became capable of infecting humans at the Wuhan seafood market
• But a 2017 article warned of the unpredictability of lab animals that scientists at the Wuhan lab intended to inject with viruses 

Scientists warned in 2017 that a SARS-like virus could escape a lab set up that year in Wuhan, China, to study some of the most dangerous pathogens in the world.

Now, a SARS-like coronavirus has infected more than 800 there, spread to at least 10 other countries and killed 25 in Wuhan and nearby provinces.

China installed the first of a planned five to seven biolabs designed for maximum safety in Wuhan in 2017, for the purpose of studying the most high-risk pathogens, including the Ebola and the SARS viruses.

Tim Trevan, a Maryland biosafety consultant, told Nature that year, when the lab was on the cusp of opening, that he worried that China’s culture could make the institute unsafe because ‘structures where everyone feels free to speak up and openness of information are important.’

In fact, the SARS virus had ‘escaped’ multiple times from a lab in Beijing, according to the Nature article.

The Wuhan National Biosafety Laboratory is located about 20 miles away from the Huanan Seafood Market and some have wondered if the outbreak’s epicentre is coincidental, but the scientific community currently believes that the virus mutated through and jumped to people through animal-human contact at the market.

But, ‘at this point there’s no reason to harbour suspicions’ that the facility had anything to do with the outbreak, besides being responsible for the crucial genome sequencing that lets doctors diagnose it, Rutgers University microbiologist Dr Richard Ebright told DailyMail.com.

China’s highest-grade lab for studying viruses is located in Wuhan, the same city at the centre of the current coronavirus outbreak

The Wuhan National Biosafety Laboratory, housed at the Wuhan Institute of Virology, was set up in the hopes of helping China contribute research on the world’s most dangerous viruses.

Constructed in 2015, the lab was still undergoing safety testing, but near ready to open in 2017.

It was the first ever lab in the country designed to meet biosafety-level-4 (BSL-4) standards – the highest biohazard level, meaning that it would be qualified to handle the most dangerous pathogens.

BSL-4 labs have to be equipped with airtight hazmat suits or special ‘cabinet’ work spaces that confine viruses and bacteria that can be transmitted through the air to sealed boxes that scientists reach into using attached high-grade gloves.

There are about 54 BSL-4 labs worldwide.

China’s first, in Wuhan, received federal accreditation in January 2017.

Upon opening, it planned to first take up a project that required only BSL-3 precautions to be in place: a tick-borne virus that causes Crimean-Congo hemorrhagic fever.

It’s as highly fatal disease, killing 10 to 40 percent of those it infects.

SARS, too, is a BSL-3 virus. According to Nature’s interview with the lab’s director, Yuan Zhimin, the Wuhan National Biosafety Laboratory planned to study the SARS virus.

In January 2018, the lab was operational ‘for global experiments on BSL-4 pathogens,’ wrote Guizhen Wu in the journal Biosafety and Health.

After a SARS virus escaped in a ‘leak’ from another lab in 2004, Chinese officials worked to improve safety, but also to expand the country’s capacity to continue to study the very viruses its lab had let out.

These Hazmat suits are intended to protect scientists from easily transmitted viruses, like those that can be caught by breathing in, while working at the Wuhan lab

‘After a laboratory leak incident of SARS in 2004, the former Ministry of Health of China initiated the construction of preservation laboratories for high-level pathogens such as SARS, coronavirus, and pandemic influenza virus,’ wrote Guizhen Wu.

It’s not clear what or where those labs were.

The Wuhan lab is also equipped for animal research.

In 2017, the scientists who spoke to Nature acknowledge the opportunity this presents for the development of vaccines and treatments.

Regulations for animal research – especially that conducted on primates – are much looser in China than in the US and other Western countries, meaning these studies are less costly and face fewer barriers that could limit or slow them.

But that was also cause for concern for Trevan.

Studying the behaviour of a virus like 209-nCoV and developing treatments or vaccines for it requires infecting these research monkeys, an important step before human testing.

Monkeys are unpredictable though, warned Ebright.

‘They can run, they can scratch they can bite,’ he said, and the viruses they carry would go where their feet, nails and teeth do.

https://www.dailymail.co.uk/health/article-7922379/Chinas-lab-studying-SARS-Ebola-Wuhan-outbreaks-center.html

Sacked Moffitt Officials Didn’t Report Chinese Financial Ties

Top officials and researchers who resigned from Moffitt Cancer Center in Tampa, Florida, last month didn’t make requisite disclosures about foreign financial ties, according to new details that emerged this week in documents released by state lawmakers.
They didn’t report personal payments or bank accounts in China that totaled hundreds of thousands of dollars in research subsidies and annual salaries, as was required by their institution and the National Institutes of Health, according to the report.
The Moffitt shake-up is the latest event in the federal government’s push to thwart intellectual property theft by China at U.S. research institutions. It was perhaps the highest-profile case yet: President and CEO Alan List, MD, and vice president and center director Thomas Sellers, PhD, resigned under pressure along with four researchers who hid their relationship with China’s Thousand Talents Program for global recruitment.
Florida lawmakers have been investigating “whether our taxpayer-supported research institutions may have been compromised or vulnerable to intellectual property theft by foreign governments.”
Shifting Tides
The NIH had encouraged and contributed to scientific cooperation with China over the past 30 years but did a recent about-face as the FBI and congressional leaders raised concerns about the risk of intellectual property and technology theft. In March 2018, the NIH clarified how serious it was about conflict of interest disclosures that any personal income or research funding from foreign institutions be reported to one’s U.S. institution.
As a result, MD Anderson Cancer Center cut ties with three scientists in April 2019 and Emory University fired two neuroscientists in May for failing to disclose foreign research ties or undermining the integrity of research funding. All five were Asian Americans, whereas only one of the six at Moffitt is ethnic Chinese.
That Moffitt researcher, immunologist Sheng Wei, MD, was a key figure in the affiliation the Florida center started in 2008 to provide training and consultation to Tianjin Medical University Cancer Institute and Hospital.
Wei was first to be recruited by the Thousand Talents Program and, in turn, recruited List and then others at Moffitt to collaborate with Tianjin Medical University. Aside from Sellers, others involved were Daniel Sullivan, MD, a director of Moffitt’s clinical science program who oversaw the Tianjin partnership, and cancer biologist Pearlie Epling-Burnette, PharmD, PhD.
Pharmacogenomicist Howard McLeod, PharmD, also fired in December from Moffitt, was already participating in the Thousand Talents Program through another Chinese institution when he came to Moffitt in 2013.
Improper Disclosure
While these relationships and even participation in the Thousand Talents Program did not violate Moffitt policies, the center and NIH regulations required timely disclosure and advance approval after assessment for possible conflicts of interest or other compliance risks.
Those disclosures didn’t happen properly, with the “possible limited exception” of McLeod, according to the report.
They didn’t report personal payments or opening or maintaining personal bank accounts in China to receive Talents program compensation that could have been as much as $142,000 up front and research subsidies of up to $711,000 along with annual salaries of $36,000 to $64,000. There were also fully-paid escorted tourist trips in China, cash honoraria for speeches, and cash travel reimbursements while in China — many not disclosed to Moffitt.
Notably, “List did not disclose to Moffitt his participation in Chinese Talents programs, any Talents program payments, or his Chinese personal bank account, until specifically asked by Moffitt’s Compliance Office in late September 2019,” the report noted.
Importantly, List and three others opened those Chinese bank accounts to get compensation in November 2018 — “at a time well after these foreign influence issues had been brought to their attention by Moffitt and by the NIH through national academic and medical community announcements and public media reports.”
Others at the University of Florida including a College of Medicine faculty member and biomedical engineer were also sacked recently for similar transgressions.
What exactly was done in exchange for the money isn’t clear, but “[t]here is no evidence to date that intellectual property has been stolen or that research or patient care has been compromised,” the report reiterated.
Moffitt has said it is “reviewing its 12-year research and education partnership with the Tianjin Medical University Cancer Institute and Hospital, a 2,400-bed hospital outside of Beijing,” as reported by the Tampa Bay Times.
Similar compliance reviews and probes are underway around the country. “At least 200 people are being investigated at 71 US hospitals, universities, and research institutions,” according to The BMJ.
https://www.medpagetoday.com/publichealthpolicy/ethics/84502

Time to Unleash Drug Treatments for Addiction

A National Academies panel on Thursday urged radical changes in state and federal law to improve treatment and prevention of opioid use disorder, which in turn would cut the nation’s infectious disease burden.
The committee’s 10 members — comprising academics, medical professionals, epidemiologists, nurses, and health policy specialists — recommended scrapping mandatory waivers for buprenorphine prescribers; eliminating prior authorization requirements for buprenorphine and all FDA-approved treatments for opioid use disorder; and allowing methadone treatment to be delivered in primary care settings.

The committee held that one reason for the “unprecedented number of HIV and viral hepatitis outbreaks” is that substance use disorder treatment is siloed from delivery of other medical care.
Also, “well-intentioned policies” such as increasing reliance on prescription drug monitoring programs, intended to curb access to prescription opioids, have had unintended consequences — sometimes driving people to illicit injected drugs such as heroin.
As the number of people who inject drugs increased, so did the risk of infectious disease.
The good news is that preventing and treating opioid use disorders can improve infectious disease outcomes, the authors noted.
For instance, patients with a co-occurring opioid use disorder and HIV will be better at complying with their HIV medication regimens if their treatment plan also includes medication for opioid use disorder.
“In this way removing barriers for opioid use disorder treatment is, in itself, a process to improve prevention, and treatment for infectious disease,” the report said.

Moreover, when substance use disorder and infectious disease services are better coordinated, co-located or, ideally, fully integrated, healthcare becomes “simpler, more accessible and patient centered.”
End DATA Waiver, Prior Authorization
One of the report’s most dramatic recommendations is to eliminate state-level prior authorization requirements for buprenorphine. The authors say this additional step delays access to evidence-based care for patients with opioid use disorder and increases the risk of infectious disease due to patients’ continued drug use.
To put federal teeth into such a policy, the Centers for Medicare & Medicaid Services should withhold approval of any requests for Medicaid state plan amendments from states that maintain prior authorization requirements, the report said.
A federal law enacted two decades ago mandates that providers seeking permission to prescribe buprenorphine complete an 8- to 24-hour training course. But the committee said this waiver “poses a barrier for some providers.”

For that reason, the committee recommended that Congress amend the legislation to drop that requirement.
In speaking with clinician prescribers, the report’s authors found that many believed the mandated training was “inadequate and clinically irrelevant.”
For that reason, the committee recommended that any organizations that currently offer training should examine its curriculum and its usefulness and “provide newly trained providers with greater access to experienced peers.”
Another recommendation: the Substance Abuse and Mental Health Services Administration (SAMHSA) should offer additional funds and grants aimed at “expand[ing] mentorship networks for providers.”
Additionally, the report called on Congress to eliminate the cap on the number of patients that prescribers can serve.
The report also addressed barriers to methadone treatment for opioid use disorder. It recommended federal legislation to let clinicians provide the drug in primary care settings. As the law now stands, methadone can only be prescribed for addiction treatment in certain licensed and regulated facilities — i.e., dedicated opioid treatment programs.

Conversely, the committee noted that with 1,600 opioid treatment programs across the country in 2018 serving 380,000 patients each year, it’s a mistake — a “missed opportunity” — that such programs do not frequently offer testing and treatment for infectious disease.
The committee therefore suggested that the Department of Health and Human Services consider instituting “universal, opt-out-testing and connection to treatment for infectious diseases,” particularly in methadone-based opioid treatment programs.
But on the thorny issue of 42 CFR Part 2, often known simply as “Part Two” — the federal rule that defines the right of access among different stakeholders to patients’ records from substance use disorder treatment programs — the committee mostly punted.
The report suggested that SAMHSA either align Part Two with the Health Insurance Portability and Accountability Act or “alter the definition of which specific service programs” are encompassed in Part Two.
“[T]here is significant debate about whether and how changing this regulation would jeopardize patient privacy or allow providers to deliver more coordinated, effective care,” the authors noted.
SAMHSA should “formally engage with patients, advocacy groups, the general public, and legal experts” to weigh the pros and cons of wider data sharing, the report concluded.

https://www.medpagetoday.com/psychiatry/addictions/84534