A team of researchers analysed centuries-old DNA samples from plague burial pits in London identified genes that protected some against the Black Death that swept through Europe, Asia and Africa nearly 700 years ago. Their study, which showed how those aspects of our immune systems have continued to evolve since that time, is published in the journal Nature.
According to the researchers’ findings, the same genes that once conferred protection against the Black Death are today linked to an increased susceptibility to autoimmune diseases such as Crohn’s and rheumatoid arthritis.
The team focused on a 100-year window before, during and after the Black Death, which reached London in the mid-1300s. It remains the single greatest human mortality event in recorded history, killing upwards of 50% of the people in what were then some of the most densely populated parts of the world.
More than 500 ancient DNA samples were extracted and screened from the remains of individuals who had died before the plague, died from it or survived the Black Death in London, including individuals buried in the East Smithfield plague pits used for mass burials in 1348–9. Additional samples were taken from remains in Denmark.
Scientists searched for signs of genetic adaptation related to the plague, which is caused by the bacterium Yersinia pestis.
They identified four genes that were under selection, all of which are involved in the production of proteins that defend our systems from invading pathogens and found that alleles of the genes either protected or rendered one susceptible to plague.
Individuals with two identical copies of a particular gene, known as ERAP2, survived the pandemic at a much higher rates than those with the opposing set of copies, because the ‘good’ copies allowed for more efficient neutralisation of Y. pestis by immune cells.
“When a pandemic of this nature – killing 30 to 50 per cent of the population – occurs, there is bound to be selection for protective alleles in humans, which is to say people susceptible to the circulating pathogen will succumb. Even a slight advantage means the difference between surviving or passing. Of course, those survivors who are of breeding age will pass on their genes,” explained evolutionary geneticist Hendrik Poinar, an author of the Nature paper.
Europeans living at the time of the Black Death had were extremely vulnerable at first as they had no recent exposure to Yersinia pestis. Mortality rates fell in subsequent waves of the pandemic over the following centuries.
Researchers estimate that people with the ERAP2 protective allele (the good copy of the gene, or trait), were 40 to 50 per cent more likely to survive than those who did not.
“The selective advantage associated with the selected loci are among the strongest ever reported in humans showing how a single pathogen can have such a strong impact to the evolution of the immune system,” says human geneticist Luis Barreiro, an author on the paper, and professor in Genetic Medicine at the University of Chicago.
The resignation of renowned breast cancer specialist surgeon Professor Carol-Ann Benn from the Helen Joseph Hospital has fuelled concerns about the loss of expertise for the public health sector amid existing pressures on cancer services in Gauteng. Concerns have also been raised about what some labelled an unconducive workplace culture and worsening working conditions at the hospital.
Some hospital insiders called the environment toxic with patriarchy and petty hierarchies. This, compounded with ongoing operational challenges, is having a dire impact on staff retention and the quality of patient care.
Benn’s last day at the clinic at the end of September brought to a close a 17-year-long relationship with the public health facility. Volunteers from the not-for-profit Breast Health Foundation which Benn is a founding director of, have backed her decision and have also ended their services at the hospital.
“The Breast Health Foundation’s decision to withdraw services in solidarity with Professor Benn comes after months of trying to address barriers to the provision of quality patient care and a lack of support from senior management,” its statement read.
Louise Turner, chief operations officer at the Foundation, says after an initial phone conversation there have been no further discussions on a way forward to restart their services there. The Foundation had five patient navigators and three volunteers based at Helen Joseph Hospital (HJH). Navigators guide patients through their journey from diagnosis to treatment, help to link them to services, and to advance them along long cancer treatment waiting lists. They also offer psycho-social counselling and become a practical support net. Spotlight previously reported on their work here.
Responding to the concerns raised, the Gauteng Department of Health, however, says no patients will be affected negatively by the exodus of Benn and the Foundation and that the clinic remains fully operational.
Spokesperson for the department, Kgomotso Mophulane, says, “The Breast Clinic is not closed at Helen Joseph Hospital. It is only one employee who has resigned but the clinic continues to have other specialists who run the clinic.”
Mophulane says that the Breast Health Foundation does not have a formal agreement with the department of health and that “existing agreements with other facilities such as Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) continue”.
If the shoe doesn’t fit
Benn has straddled public and private healthcare throughout her 30-year career and she remains head of the Netcare Breast Care Centre and continues to lecture at Wits University’s department of surgery.
“My patients have taught me so much over the years,” says Benn. “Leaving Helen Joseph after 17 years has been a struggle. There was harassment and an obstructive workplace culture that made our daily working lives impossible, but I can’t spend my time getting into trouble for trying to find solutions. And if my patients have to face so much to survive, then I can survive this too.”
Benn says she’s “stepping outside to find solutions”. She says her next focus is to find ways to reform access for cancer treatment on lower-level medical aid schemes without massive co-payments and her work in the public sector continues. Benn says she is managing her existing Helen Joseph patients at her practice at Milpark Hospital and says she’s already had positive advances to set up a “patient-centered unit for equitable care for public patients within the private sector” that will be ready to launch within the next few weeks.
“I don’t fit the shoe of government but I’m leaving to innovate in other ways because no one should be turned away from a specialist unit because they don’t have the money or because they don’t live in a catchment area.”
According to Helen Joseph Hospital CEO Dr Relebohile Ncha, Benn had raised issues of “challenges she had with her supervisor, which is one of the clinical managers. Unfortunately, these issues were brought forward at the time of her resignation and therefore there was no time to redress [sic] the issues raised directly with her.”
Ncha adds that the labour relations department would have dealt with the “workplace relationship challenges”. She also says the psychology department will provide counselling for cancer patients in the absence of the Foundation.
According to Ncha, the system in place remains that new patients are seen on a Tuesday for diagnosis and are “booked within a week” for further treatment. Ncha says there are currently between 400 and 550 outpatients and between 20 and 30 patients booked for surgery per month. She also says there are no oncology specialists at Helen Joseph Hospital, as this care is referred to CMJAH.
A long history
According to Turner, the Breast Health Foundation over the years has helped turn the clinic into a hub of excellence. “So much of what is in the clinic we raised money for – from painting the walls, décor, to the chairs and furniture in the counselling rooms.”
Turner says they’ve helped around 200 000 patients to be “navigated” through the maze of cancer diagnosis and treatment at the facility and around 10 000 people who were diagnosed with cancers were supported through their journey of ups and downs of cancer treatment.
But she says it was clear the workplace environment had become increasingly untenable for Benn and also the Foundation’s team. According to Turner, Benn was being summoned to meetings constantly from the hospital floor to answer for her decisions and was criticised and undermined for veering off administrative procedures.
“Professor Benn’s approach has always been about putting the patient first. She has used her own money to buy things like surgical drains or surgical gloves so that she could do her work. She always made a plan, including squeezing in surgeries and she did accept patients who do not fall into the Helen Joseph catchment area because of their need to access services. But senior management would make her life hell unnecessarily over this,” she says.
‘a family of survivors’
Patient navigator for the Breast Health Foundation Ouma Mamatela was a patient of Benn in 2016 before she joined the Foundation. She says patients at HJH are now paying the price for “egos and mismanagement”.
“It’s going to be very, very hard for patients who expect to find the navigators there to hold their hand through everything. We built up a family of survivors. I am still waking up very early on Tuesdays and Thursdays because those were the days I knew I was getting up to serve our patients at Helen Joseph,” says Mamatela.
Ouma Mamatela, cancer survivor and cancer patient navigator. PHOTO: Rosetta Msimanga/Spotlight
She adds that Benn’s out-of-the-box thinking, accessibility to patients, and transparency in the way she worked irked senior male managers and doctors.
“Professor Benn is one person who speaks to everyone. She doesn’t make herself untouchable. I want to say to those managers that they need to put their egos aside because it is the patients that need quality care the most who are suffering,” she says.
‘you can feel that it’s different now’
Twenty-six-year-old *Thandiwe was one of Benn’s last patients at Helen Joseph. Her mother *Thawe says that she and her daughter have experienced both kindness and professional care from Benn and the Foundation and have also borne the brunt of bureaucratic pettiness and outright bullying from senior clinical management at the hospital.
Thawe asked for their identities to be protected, fearful of being victimised at the hospital.
Thawe tells first how her family’s world came to a crashing halt when Thandiwe found a lump in her breast in July this year. Thandiwe, who was living in the North West province at the time, had a biopsy done at the Moses Kotane District Hospital but says she never received her results.
Being unwell she couldn’t keep her job and eventually came to Johannesburg to be with her mom. Thawe’s employer donated R10 000 towards her daughter’s treatment.
“When I asked in the office and googled about where I could get help, the name that kept coming up was Professor Benn’s so we decided to use the money to do another biopsy and to see Professor Benn at her private practice in Milpark.
“When we saw the Prof she was so kind and informative. She explained everything and gave us some peace even when she confirmed that Thandiwe was cancer-positive. When it came time to pay, she realised that we didn’t have medical aid so she told the receptionist not to charge us anything,” says Thawe.
Benn told them to come to her clinic day at Helen Joseph so the next steps of surgery could begin. Benn also advised plastic surgery at the same time as the removal of the cancerous lump would significantly reduce the size of Thandiwe’s left breast.
On the clinic day, Thawe says they waited for hours but she adds, “Everyone from the Foundation was friendly and explained what was happening. When it’s like that you accept that you have to wait.”
But then Thawe was told her daughter would not be admitted for surgery and that her case was being referred to Charlotte Maxeke Johannesburg Academic Hospital instead.
“Another doctor took Thandiwe off the surgery list and sent a junior doctor to us with the referral letter without any explanation,” she says.
At Charlotte Maxeke, she says Thandiwe was sent from department to department and could not get admitted there either. Eventually, a desperate Thawe returned to Helen Joseph to demand an explanation.
“I was taken to see these three men in the clinical manager’s office. They showed no empathy – they just didn’t care. They just kept saying ‘wrong catchment area’, that they could not do the plastic surgery at Helen Joseph, and that Benn should never have told us to come to Helen Joseph,” she says.
Thawe and Thandiwe stayed in contact with Benn. Mother and daughter kept fighting and eventually took their complaint to hospital CEO Ncha. Only then was Thandiwe’s surgery approved.
She says Benn kept her promise to operate on Thandiwe and also made arrangements with a plastic surgeon from Charlotte Maxeke to help with the reconstructive surgery for Thandiwe.
“I cannot find the words to thank Professor Benn for all she did to save my daughter’s life,” Thawe says.
But she says since Benn and the Foundation’s exodus at the end of September, “it’s been a mess at Helen Joseph”. She accompanied Thandiwe to have a drain removed and her bandages and dressings changed at the beginning of October. “All those ladies in pink that used to help us were gone. All the patients were just sitting without knowing what was happening and no one telling us anything. When we eventually saw a doctor she said she didn’t know how to remove the drains. She took some photos of Thandiwe and told us to come back the next day.
“I had to change Thandiwe’s bandages myself and tell the nurses how to tape the drain. You can feel that it’s different now without Benn and the navigators,” she says. Eventually, they were forced to go to Charlotte Maxeke where the plastic surgeon that operated on Thandiwe helped to remove the drain properly. “It’s been hell at HJH – I worry for what will happen to other women who cannot fight like we did,” she says.
Dozens of Helen Joseph patients have also since weighed in via social media in support of Benn and the Foundation, sharing their stories and also their deepening worries about what comes next for their treatment.
**Patients needing to get in touch with the Breast Health Foundation can continue to do so via their support line on 0860 283 343.
Chronic back pain, a pervasive complaint in modern society, has many treatments including physiotherapy. A meta-analysis published in theJournal of Pain, has delivered new insights into the most effective therapies for back pain and revealed that individualised exercise treatments were quite effective, especially when combined with cognitive behavioural therapy.
The researchers analysed 58 randomised controlled trials (RCTs) of over 10 000 patients worldwide with chronic low back pain. First, the data relevant to the topic were filtered out of the original manuscripts and then evaluated in groups. When evaluating these data, the researchers examined on the one hand whether and to what extent standard forms of treatment and individualised treatment differ in terms of the result. “Individualised” means that there is some type of personal coaching, where therapists specifically target the potentials and requirements of each patient and decide together with them how their therapy should look.
The study concluded that individualised treatment for chronic back pain led to a significantly increased effect in comparison to standard exercise therapies. The success rate in pain relief was 38% higher than with standard treatment. “The higher effort required for individual treatment is worthwhile because patients benefit to an extent that is clinically important,” says lead author Dr Johannes Fleckenstein from the Institute of Sport Sciences at Goethe University Frankfurt.
The research team then compared a third group of treatment methods alongside the standard and individualised ones. In this group, individualised training sessions were combined with cognitive behavioural therapy (CBT). This procedure is based on the assumption that negative thoughts and behaviours surrounding pain tend to exacerbate it. Through CBT, pain patients learn to change the way they handle it. They stop being afraid to move or are taught tactics for coping with pain. This makes them realise that they are by no means helpless. But what does the psychotherapeutic support through CBT actually contribute to the success of the treatment? Analysis of the data revealed the following: when an individualised approach and CBT were combined, the success rate in terms of pain relief was an impressive 84% higher than with standard treatment. The combined therapy, also called multimodal therapy, thus led to the best result by far.
Dr Fleckenstein sees in the study “an urgent appeal to public health policy” to promote combined therapies both in terms of patient care and remuneration. “Compared to other countries, such as the USA, we are in a relatively good position in Germany. For example, we issue less prescriptions for strong narcotic drugs such as opiates. But the number of unnecessary X-rays, which, by the way, can also contribute to pain chronicity, and inaccurate surgical indications is still very high.” This is also due, Dr Fleckenstein said, to economic incentives for such interventions. The situation is different for organisations working in the area of pain therapy, he said. Although these are not unprofitable, they are not a cash cow for investors either. In his view, it is important here to improve the economic conditions. After all, pain therapy saves a lot of money in the long run as far as health economics are concerned, whereas tablets and operations rarely lead to medium and long-term pain relief.
People with fibrotic interstitial lung disease that has no obvious cause are more likely to die if they live in areas with higher levels of air pollution composed of chemicals associated with industrial sources and vehicular traffic, according to new published today in JAMA Internal Medicine.
The University of Pittsburgh study is the first to link the chemical composition of fine particulate air pollution to worsened fibrotic interstitial lung disease (fILD) outcomes. It is also the largest study ever done to evaluate the impact of air pollution on these patients.
“Some people with these lung diseases have an expected lifespan from diagnosis to death of only a few years, and yet it’s a mystery as to why they developed the disease, why their lungs become so scarred,” said lead author Gillian Goobie, MD, doctoral candidate. “Our study points to air pollution – specifically pollutants from factories and vehicles – as potentially driving faster disease progression and premature death in these patients.”
Goobie and her team obtained data from 6,683 patients with fILDs in the U.S. and Canada and linked their home addresses with satellite and ground-monitoring air pollution data to determine air pollutant composition to an accuracy of less than half a mile.
The team specifically looked at a pollutant known as PM2.5, which refers to particulate matter that measures less than 2.5 microns across, a size invisible to the naked eye. This type of pollution is so small that it can infiltrate deep into the lungs and even cross into the blood stream, where it can contribute to other diseases outside of the lungs, such as heart disease.
“In the past, most environmental health research has focused on the simple definition of PM2.5 as anything of that size,” said co-author James Fabisiak, Ph.D., associate professor in Pitt Public Health’s Department of Environmental and Occupational Health. “But PM2.5 is chemically diverse, with a different composition depending on whether it came from a forest fire or a tailpipe. Research has lacked in determining if the type of PM2.5 matters when it comes to health effects. Our new research is a big step toward filling in that knowledge gap.”
The team found that increasing levels of PM2.5 were linked to more severe disease at diagnosis, faster disease progression as measured by lung function decline and higher likelihood of dying sooner. Pollution high in sulfate (typically produced by factories, such as the coal and steel industries), nitrate (primarily from fossil fuel combustion) and ammonium (usually produced by industry or agriculture) were associated with worse outcomes, whereas chemical signatures from more naturally occurring particulate matter such as sea salt or soil dust didn’t carry as high of an association.
After pollution leaves a smokestack or tailpipe, Goobie noted that sulfate- and nitrate-containing aerosols can be formed in the atmosphere from those and other gaseous pollutants and can be acidic, which can be very damaging to the tiny air sacs of the lungs.
The team is now doing laboratory studies looking at the impact of these pollutants on lung cells at the molecular level to better understand why they are particularly damaging to the lungs of certain people and whether exposure to the pollutants triggers changes to how certain genes work that could cause runaway scarring.
According to the team’s calculations, if exposure to industrial pollutants hadn’t occurred, most premature deaths among participants living in areas of North America with a heavier burden of industry could have been avoided. Participants of colour were disproportionately exposed to higher levels of human-made air pollutants: 13% of the high-exposure group were non-white, but only 8% of the low-exposure group, highlighting the impact of environmental injustice in these findings as well.
Co-senior author S. Mehdi Nouraie, MD, PhD, associate professor of pulmonary, allergy and critical care medicine at Pitt’s School of Medicine, said that the findings further emphasise the need for people with lung conditions that make them more vulnerable to pollution to pay attention to the air quality index and consider minimising time outdoors or in rooms without good air filtration during poor air quality days.
“Ultimately, we want to encourage a data-driven awareness,” A/Prof Nouraie said. “We want people to think about the quality of the air we breathe. Patients, health care providers and policymakers can all use the new information we’re providing to try to improve health outcomes. When you make the air safe for the most vulnerable to breathe, you’re making it safe for all of us.”
For men and women, the risk factors for cardiovascular disease are largely the same, an extensive global study involving over 155 000 participants shows.
The study, published in The Lancet, includes participants from 21 countries with differing GDP. Cardiovascular disease is more widespread in low- and middle-income countries.
The 21-country study used data were taken from the Prospective Urban Rural Epidemiological (PURE) Study and comprised 155 724 participants aged 35–70 years with no history of cardiovascular disease when they joined the study. All cases of fatal cardiovascular disease, heart attack, stroke, and heart failure during the follow-up period, which averaged ten years, were registered.
The risk factors studied were metabolic (such as high blood pressure, obesity, and diabetes), behavioral (tobacco smoking and diet), and psychosocial (economic status and depression).
No clear gender or income divide
Metabolic risk factors were found to be similar in both sexes, except for high values of low-density lipoprotein (LDL, often known as bad cholesterol), where the association with cardiovascular disease was stronger in men. In the researchers’ opinion, however, this finding needs confirmation in more studies.
Depressive symptoms were another risk factor for cardiovascular disease that proved to be more significant among the men than the women. On the other hand, the link between a poor diet and cardiovascular disease was closer in women; and smoking, though markedly more frequent among men, was just as injurious a risk factor for women.
Overall, the researchers found broadly similar risk factors for cardiovascular disease for the male and female participants, irrespective of their countries’ income level. This highlights the importance of disease prevention strategies, too, being the same for both sexes.
Similarities greater than differences
The women’s lower overall risk of cardiovascular disease, especially heart attack (myocardial infarction), may be explained by the younger women’s higher tolerance to risk factors. Their estrogen makes vessel walls more compliant and affects the liver’s capacity to get rid of LDL.
Among the 90 934 women in the study, 5.0 cases of stroke, heart attack, and/or cardiovascular disease were registered per 1000 persons per year. The corresponding number in the group of men (64 790 individuals) was 8.2 cases.
Annika Rosengren, Professor of Medicine at Sahlgrenska Academy, University of Gothenburg, is the second author of the study, in charge of the Swedish part of the PURE population study of 4 000 individuals in Gothenburg and Skaraborg.
“When it comes to cardiovascular disease in men and women, the similarities in terms of risk factors are considerably greater than the differences. But men are more vulnerable to high levels of LDL, the bad cholesterol, and we know from other studies that they develop pathological changes in the coronary arteries at a lower age than women, and tend to start developing myocardial infarction quite a lot earlier. With respect to early stroke, though, the sex differences are less pronounced, as we’ve also seen in other studies,” Prof Rosengren said.
Researchers have found that rheumatoid arthritis drug auranofin can potentially be repurposed to improve diabetes-associated symptoms. The study, which used a mouse model, appeared in the journal Cell Metabolism.
Although clear links have been identified between inflammation in white adipose tissue and insulin resistance in humans and rodents, broad anti-inflammatory treatments lack durable clinical efficacy on diabetes. In the current study, the researchers delved deeper into this association between inflammation and diabetes by looking for existing drugs that might affect both conditions.
“We computationally screened a small-molecule dataset and identified auranofin, an FDA-approved drug that has been used to treat rheumatoid arthritis, a condition involving inflammation,” said first and co-corresponding author Dr Aaron R. Cox, instructor of medicine-endocrinology, diabetes and metabolism at Baylor. “Auranofin exerts anti-inflammatory properties, which many people suspected would be beneficial in obesity and diabetes; however, nothing was really known about how it might affect metabolism.”
The team evaluated the metabolic effects of auranofin in a mouse model of diabetes in which the animals consume a high-fat diet.
“We discovered that auranofin has anti-inflammatory and anti-diabetic effects that are independent from each other,” said co-corresponding author Dr Sean Hartig, associate professor at Baylor. “Auranofin improved insulin sensitivity, or the body’s ability to respond to insulin to keep blood sugar at healthy levels. The drug also normalised obesity-associated changes such as hyperinsulinaemia in the mouse model. In addition, we found that auranofin accumulation in white adipose tissue reduced inflammatory responses without altering body composition in obese mice.”
Looking into the mechanism of these metabolic changes, the team discovered that auranofin’s anti-diabetic effects involved reduction of leptin levels. Leptin is a hormone whose levels markedly increase in obesity, contributing to insulin resistance and diabetes. In addition, auranofin restored white adipose tissue’s ability to respond to catecholamines, which are signals that increase metabolic activities in adipose tissue, triggering the burning of lipids at a higher rate.
“These changes coupled together contribute to the overall improvement in insulin sensitivity of the mice, leading to blood glucose control, which is the ultimate goal of diabetes treatments,” Dr Cox said. “High levels of glucose in the blood are detrimental to many tissues in the body. Uncontrolled, diabetes can lead to organ failure.”
Researchers in the American Journal of Epidemiology report that wastewater surveillance of diseases that infect humans should work in most cases. But more research is needed to apply the science for public health benefit, the research team concluded.
Led by epidemiologist David Larsen from Syracuse University, the team’s work published examined all peer-reviewed scientific articles of wastewater surveillance published through July 2020. The team identified a variety of pathogens that can be found in wastewater, including almost all infectious diseases that the World Health Organization has classified as a Public Health Emergency of International Concern (PHEIC) such as Ebola virus and Zika virus.
But despite this positive finding, few studies relate what is found in the wastewater to public health and the amount of disease that is circulating.
“Testing the wastewater is only one component of this powerful science,” said Dr Larsen, an associate professor of public health at Syracuse University. “Understanding the results and implications for public health is just as challenging. We need interdisciplinary teams working together to maximise the benefit of wastewater-based epidemiology.”
Wastewater-based epidemiology is the science of taking what is found in wastewater and using that information to understand population-level health trends. Most of the articles reviewed looked at what they could find in the wastewater and omitted the second step of relating the findings to other measures of population-level health, such as numbers of cases, test positivity, or hospitalisations.
Wastewater-based epidemiology of COVID has enjoyed substantial availability of clinical COVID data, and results from wastewater surveillance are more easily understood in terms of COVID transmission. However, the research team determined that more work is needed to be done for other pathogens, including monkeypox and polio, to increase the utility of wastewater surveillance to benefit public health.
The prognosis for breast cancer has improved, allowing more and more women to be cured with a combination of surgery, radiotherapy and medical treatment. A new trial led by Karolinska Institutet will investigate whether combining neoadjuvant chemotherapy with exercise will improve the outcomes of breast cancer patients.
Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The main benefit of NACT is its ability to downstage large tumours with a view to treatment by breast-conserving surgery, although there is a non-significant increase in the local recurrence rate. The best proof of NACT efficacy is pathological complete response (pCR), ie the absence of invasive tumour on post-NACT on surgical histopathology.
“While it is known that physical exercise can help patients to better tolerate often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes”, explained Jana de Boniface, principal investigator of the trial and associate professor in the Breast Surgery Group, Department of Molecular Medicine and Surgery.
The Neo-ACT trial opened for recruitment in September 2022, and it is estimated that inclusion may be completed in December 2025.
The pharmaceutical industry is facing a serious challenge as it struggles to source enough non-human primates (NHPs) such as macaques for research and testing. Alongside demand created by HIV/AIDS research, the pandemic has tightened supplies of the animals further as China, a major supplier, has clamped down on exports.
Since NHPs have great genetic and physiological similarity to humans, scientists use these animals, most commonly rhesus macaques, to study medical conditions and conduct trials which are not yet possible in humans. In 2019, US scientists used 68 257 NHPs in research, according to US government data.
As a result of this shortage, many projects may not be able to be completed, according to industry insiders, with implications for medical research. Pre-pandemic prices of $11 000 per macaque have risen to $35 000.
In July last year, Nature reported that the US government pledged to increase funding to make primates available for clinical research. However, this would not do anything to address the current shortage.
To make room for more NHPs, the US National Institutes of Health (NIH) has invested about US$29 million to refurbish housing, build outdoor enclosures and making other infrastructure improvements at the US National Primate Research Centers (NPRCs), which it funds.
“A couple of years ago, we were feeling the pinch,” Nancy Haigwood, director of the Oregon NPRC in Beaverton, which houses about 5 000 non-human primates. But because of the pandemic, “we are truly out of animals”, she told Nature. “We’re turning away everyone.”
China had been a cheap source of cynomolgus macaques (Macaca fascicularis) since 1985, but in 2013 began to prioritise local research, restricting exports. Adding to this was soaring demand was sparked by multiple NIH grants awarded in 2016 to study HIV/AIDS, according to a 2018 report. Housing and feeding NHPs is costly, and NPRCs could not expand due to budget caps. The report warned of a coming shortage of various primates in coming years.
The situation has drawn the public’s attention – and opposition. Complaints made to airlines has resulted in many no longer carrying the animals, making transportation a major challenge. Air France was one of the last holdouts, and last year said it would stop carrying NHPs for research purposes.
With the arrival of the pandemic and the need for NHP research and testing, vaccine research was naturally prioritised, while trying to supply other projects as well.
When COVID hit, China completely suspended exports of macaques, hitting pharmaceutical companies hardest, which prefer that species for drug trials. Even if the export ban were to be lifted, the Chinese demand for macaques in research is so high that there would be few available for export: of 30 000 macaques that became suitable for use in research last year, 28 000 were used.
Other restrictions constrain the supply, such as a European Union requirement that all non-human primates for research come from self-sustaining colonies by November this year. The UK also carried through this directive following its exit from the EU.
Pregnant smokers reduced their smoking by an average of one cigarette per day before becoming aware they were pregnant, according to a new study in in Addiction Biology. In the month after learning of their pregnancy, participants reduced smoking by another four cigarettes per day.
“Our findings suggest that pregnancy could curb smokers’ desire to smoke before they are even aware of having conceived,” said the study’s lead author and principal investigator, Dr Suena Huang Massey, associate professor of psychiatry and behavioural sciences and medical social sciences at Northwestern University Feinberg School of Medicine.
“While recognition of pregnancy is a common motivation to reduce or quit smoking, if biological processes in early pregnancy are also involved as suggested by this study, identifying precisely what these processes are can lead to the development of new smoking-cessation medications.”
The vast majority of research in this field focuses on the impact of a person’s smoking on the pregnancy and the baby. This study examines, instead, the impact of pregnancy on a person’s smoking behaviour.
Though it is well known that smoking is reduced in pregnancy, it was not known when it started and whether the smokers knew they were pregnant.
“Before this paper, it was largely assumed that the only thing causing pregnant smokers to cut down was a desire to protect the baby,” Dr Massey said. “While our study does support the discovery of pregnancy as a salient event, levels of pregnancy smoking began to decline before smokers suspected they were pregnant.”
These findings support a new line of research into what happens biologically during pregnancy that might be interrupting addictive behaviours, Massey said. Her hope is that the answer to this question will lead to the discovery of new and improved ways to treat addiction.
Pregnancy hormones a contributing factor?
Human chorionic gonadotropin (hCG) is a hormone produced by the placenta in early pregnancy that is linked to morning sickness (nausea and vomiting during pregnancy).
“Strikingly, we observed the steepest declines in smoking precisely when hCG levels typically peak – between five and 10 weeks of pregnancy,” Massey said. “What’s more, pregnant smokers who do not quit during the first trimester (when hCG levels are elevated) are unlikely to quit before delivery, even with assistance from medications or financial incentives.”
Study methodology
Scientists estimated changes in cigarettes per day smoked, reported retrospectively, by 416 participants from two independent cohorts (145 from 2000 to 2005 and 271 from 2006 to 2009). Every participant was a smoker prior to becoming pregnant. Women in the study were interviewed about their smoking habits at 16 weeks of pregnancy and provided urine samples, so researchers could verify their reports.
On average, participants smoked about 10 cigarettes per day before conception. Between conception and the date they realised they were pregnant (highly variable and reported by each participant), smoking fell by an average of one cigarette per day. In the month after recognising the pregnancy, smoking dropped from an average of 9 cigarettes per day to five. Importantly, these declines were seen whether pregnancies were planned or unplanned, and whether smokers quit or did not quit.
