This comes as research suggests the risk of severe outcomes from infection is significantly higher for pregnant women compared to the general population. At the same time, data from pregnant women who have already been vaccinated around the world have shown no safety concerns associated with COVID-19 vaccines.
Vaccination during pregnancy may also protect the baby. Research has identified antibodies in cord blood and breast milk, suggesting temporary protection (passive immunity) for babies before and after birth.
This is similar to influenza and whooping cough vaccines given during pregnancy to protect pēpi. There are no safety concerns for breastfeeding women receiving a COVID-19 vaccine, and women trying to become pregnant do not need to delay vaccination or avoid becoming pregnant after vaccination.
Prioritising pregnant women
When the New Zealand government announced its vaccine rollout plan in March, pregnant women were designated as a priority in the third group, which includes 1.7 million people who are at higher risk if they catch COVID-19.
This decision reflected the available information at the time from international research showing pregnant women with COVID-19 were more likely to be hospitalised and admitted to intensive care, compared to the rest of the population.
The higher risk of hospitalisation is similar to other priority populations, including people aged 65 and over, and those with underlying health conditions or disabilities. People in these groups are also more likely to get very sick if they get COVID-19.
New Zealand’s decision was part of a principled strategy that aims to provide fair and equitable care based on scientific evidence, acknowledging research that places pregnant women in a high-risk group if they were to be infected.
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) published similar early advice, stating that women could choose to have the vaccine at any stage of pregnancy, particularly if they were in a high-risk population. But they did not recommend routine universal vaccination if levels of community transmission were low.
So what has changed since March? It became urgent to review the early advice as local vaccination centres have started vaccinating people in the third group of the rollout. Also, travel bubbles with Australia and the Cook Islands meant people were possibly more exposed to transmission.
The early advice in New Zealand and Australia was also diverging from other countries, such as Canada. And more research is coming out about the risks of COVID-19 infection in pregnancy, while international experience with mRNA-based vaccines (such as Pfizer-BioNTech) in pregnant women is growing.
Pregnant women were not included in the original clinical trials to test COVID-19 vaccines for safety. But there is no evidence of any harm associated with the vaccine during pregnancy.
Vaccine trials in the US are now actively recruiting pregnant women. We can expect research results by the end of this year. In the meantime, we can be reassured by registries, which are studies that track women who have had the vaccine during pregnancy and have given consent to have information collected about them and their babies.
Researchers in the US found women who received the vaccine during pregnancy had outcomes similar to background rates for the mother (regarding rates of miscarriage, diabetes, high blood pressure) and the baby.
Side effects from receiving the vaccine were also the same in pregnant and non-pregnant women, and it is safe to take paracetamol as needed to manage these.
Other countries, including the UK, have published decision aids to help with this important decision. I encourage professional groups to create one for New Zealand women planning or going through pregnancy.
Research supports routinely offering the vaccine to pregnant women, and it is up to individuals to decide whether to receive it or not, as part of a shared decision-making process with their midwife or doctor.
The high efficiency of protection against severe disease, the safety seen in clinical trials and the speed with which the vaccines were designed are set to transform how we develop vaccines in the future.
Once researchers have set up the mRNA manufacturing technology, they can potentially produce mRNA against any target. Manufacturing mRNA vaccines also does not need living cells, making them easier to produce than some other vaccines.
So mRNA vaccines could potentially be used to prevent a range of diseases, not just COVID-19.
Remind me again, what’s mRNA?
Messenger ribonucleic acid (or mRNA for short) is a type of genetic material that tells your body how to make proteins. The two mRNA vaccines for SARS-CoV-2, the coronavirus that causes COVID-19, deliver fragments of this mRNA into your cells.
Once inside, your body uses instructions in the mRNA to make SARS-CoV-2 spike proteins. So when you encounter the virus’ spike proteins again, your body’s immune system will already have a head start in how to handle it.
So after COVID-19, which mRNA vaccines are researchers working on next? Here are three worth knowing about.
1. Flu vaccine
Currently, we need to formulate new versions of the flu vaccine each year to protect us from the strains the World Health Organization (WHO) predicts will be circulating in flu season. This is a constant race to monitor how the virus evolves and how it spreads in real time.
The researchers used the vast amounts of data on the influenza genome to find the mRNA code for the most “highly conserved” structures of the virus. This is the mRNA least likely to mutate and lead to structural or functional changes in viral proteins.
They then prepared a mixture of mRNAs to express four different viral proteins. These included one on the stalk-like structure on the outside of the flu virus, two on the surface, and one hidden inside the virus particle.
Malaria arises through infection with the single-celled parasite Plasmodium falciparum, delivered when mosquitoes bite. There is no vaccine for it.
However, US researchers working with pharmaceutical company GSK have filed a patent for an mRNA vaccine against malaria.
The mRNA in the vaccine codes for a parasite protein called PMIF. By teaching our bodies to target this protein, the aim is to train the immune system to eradicate the parasite.
There have been promising results of the experimental vaccine in mice and early-stage human trials are being planned in the UK.
This malaria mRNA vaccine is an example of a self-amplifying mRNA vaccine. This means very small amounts of mRNA need to be made, packaged and delivered, as the mRNA will make more copies of itself once inside our cells. This is the next generation of mRNA vaccines after the “standard” mRNA vaccines seen so far against COVID-19.
But the flexibility of mRNA vaccines lets us think more broadly about tackling cancers not caused by viruses.
Some types of tumours have antigens or proteins not found in normal cells. If we could train our immune systems to identify these tumour-associated antigens then our immune cells could kill the cancer.
Cancer vaccines can be targeted to specific combinations of these antigens. BioNTech is developing one such mRNA vaccine that shows promise for people with advanced melanoma. CureVac has developed one for a specific type of lung cancer, with results from early clinical trials.
Then there’s the promise of personalised anti-cancer mRNA vaccines. If we could design an individualised vaccine specific to each patient’s tumour then we could train their immune system to fight their own individual cancer. Several research groups and companies are working on this.
Yes, there are challenges ahead
However, there are several hurdles to overcome before mRNA vaccines against other medical conditions are used more widely.
Current mRNA vaccines need to be kept frozen, limiting their use in developing countries or in remote areas. But Moderna is working on developing an mRNA vaccine that can be kept in a fridge.
Researchers also need to look at how these vaccines are delivered into the body. While injecting into the muscle works for mRNA COVID-19 vaccines, delivery into a vein may be better for cancer vaccines.
The vaccines need to be shown to be safe and effective in large-scale human clinical trials, ahead of regulatory approval. However, as regulatory bodies around the world have already approved mRNA COVID-19 vaccines, there are far fewer regulatory hurdles than a year ago.
The high cost of personalised mRNA cancer vaccines may also be an issue.
Finally, not all countries have the facilities to make mRNA vaccines on a large scale, including Australia.
Regardless of these hurdles, mRNA vaccine technology has been described as disruptive and revolutionary. If we can overcome these challenges, we can potentially change how we make vaccines now and into the future.
While COVID-19 has highlighted the value of medical research, it has unfortunately also seriously disrupted it. Lack of funding is driving members of Australia’s once-vibrant virology research community out of the sector, and forcing early-career researchers to turn to fundraising or philanthropy amid intense competition for federal government grants.
This disruption disproportionately affects early- and mid-career researchers (EMCRs) and laboratory-based scientists, especially women (who typically also shoulder the bulk of caring and home-schooling responsibilities).
In Australia, national funding of medical research happens mainly via the National Health and Medical Research Council. Over the past ten years there has been near stagnant investment, leading to a decline in funding in real terms. In 2019, the average success rates across the main NHMRC Ideas and Investigator Grant schemes was just 11.9%.
Eureka Prize-winning cancer biologist Darren Saunders and clinical geneticist Luke Hesson have both decided to leave academia altogether. The full-time medical research workforce declined by 20% between 2012 and 2017.
How did we get here?
In 2018, following extensive consultation, the NHMRC funding scheme was overhauled with major objectives to encourage innovation across the sector, reduce the burden on applicants and reviewers, and improve success rates of EMCRs.
Schemes specifically designed to develop emerging talent are also receiving dwindling support. In 2017 the NHMRC awarded 181 “early career and career development fellowships”; by 2020 that figure had fallen to 122.
The 2019 success rate for NHMRC Ideas Grants scheme (which sustains fundamental research, including on vaccines) in Australia was only 11.1%, despite almost three times as many applications being ranked as “fundable” by expert peer reviewers.
Onus on universities
With such low success rates, it has fallen to universities to prop up their research departments and laboratories.
AAMRI president Jonathan Carapetis said the lack of grants and fellowships has forced EMCRs to rely on philanthropy or fundraising to support their research, adding:
…due to the economic downturn resulting from COVID-19 the holes in this imperfect system have turned into chasms. These are the researchers who have finished their PhDs, are testing hypotheses on what causes different diseases, developing new treatments and vaccines… Our EMCRs are tomorrow’s scientific leaders, and without action to support them we will lose them.
The federal government’s Medical Research Future Fund (MRFF) was established in 2015 and began dispensing funds in 2017. As the MRFF website explains, the government uses some of the net interest from the A$20 billion fund to pay for medical research. This year it will disperse around A$650 million.
The MRFF represented a major and very welcome funding boost to Australia’s health and medical research sector.
This is a fraction of the 3% of health expenditure that would bring Australia’s health and medical research spending into line with other OECD countries. An increase to 3% of health expenditure would generate A$58 billion in health and economic benefits, according to a Deloitte Access Economics report commissioned by the Australian Society for Medical Research.
What’s more, researchers who narrowly missed out on the incredibly competitive NHMRC Investigator funding cannot apply to the MRFF unless they are a clinical researcher, meaning fundamental biomedical researchers engaged in translational research, but without a medical degree, miss out.
Without investment, advances are not possible
In the post-COVID era, a robust health and medical research sector is essential to lead the discoveries and innovations that will fuel our long-term economic recovery.
at least a doubling of federal funds into the Australian health and medical research sector
transparent, 360-degree oversight of the targeted calls for expression of interest and allocation of funds from the MRFF with involvement of NHMRC peer review.
strictly equal support for clinical and fundamental biomedical research.
This investment would position Australia as an international leader in health and medical research. Without better support for the sector, advances in patient treatment and care are simply not possible.
This article originally stated Darren Saunders and Luke Hesson have left science altogether. They have in fact decided to continue their scientific research careers outside academia. This has been corrected.
The Thousand Talents Plan is a Chinese government program to attract scientists and engineers from overseas. Since the plan began in 2008, it has recruited thousands of researchers from countries including the United States, the United Kingdom, Germany, Singapore, Canada, Japan, France and Australia.
While many countries try to lure top international research talent, the US, Canada and others have raised concerns that the Thousand Talents Plan may facilitate espionage and theft of intellectual property.
Why are we hearing about it now?
China has long been suspected of engaging in hacking and intellectual property theft. In the early 2000s, Chinese hackers were involved in the downfall of the Canadian telecommunications corporation Nortel, which some have linked to the rise of Huawei.
These efforts have attracted greater scrutiny as Western powers grow concerned about China’s increasing global influence and foreign policy projects such as the Belt and Road Initiative.
Last year, a US Senate committee declared the plan a threat to American interests. Earlier this year, Harvard nanotechnology expert Charles Lieber was arrested for lying about his links to the program.
In Australia, foreign policy think tank the Australian Strategic Policy Institute recently published a detailed report on Australian involvement in the plan. After media coverage of the plan, the parliamentary joint committee on intelligence and security is set to launch an inquiry into foreign interference in universities.
The Chinese Communist Party (CCP) developed the Thousand Talents Plan to lure top scientific talent, with the goal of making China the world’s leader in science and technology by 2050. The CCP uses the plan to obtain technologies and expertise, and arguably, Intellectual Properties from overseas by illegal or non-transparent means to build their power by leveraging those technologies with minimal costs.
China’s technology development and intellectual property portfolio has skyrocketed since the launch of the plan in 2008. Last year China overtook the US for the first time in filing the most international patents.
What are the issues?
The plan offers scientists funding and support to commercialise their research, and in return the Chinese government gains access to their technologies.
In 2019, a US Senate committee declared the plan a threat to American interests. It claimed one participating researcher stole information about US military jet engines, and more broadly that China uses American research and expertise for its own economic and military gain.
Dozens of Australian and US employees of universities and government are believed to have participated in the plan without having declared their involvement. In May, ASIO issued all Australian universities a warning about Chinese government recruitment activities.
On top of intellectual property issues, there are serious human rights concerns. Technologies transferred to China under the program have been used in the oppression of Uyghurs in Xinjiang and in society-wide facial recognition and other forms of surveillance.
A global network
The Chinese government has established more than 600 recruitment stations globally. This includes 146 in the US, 57 each in Germany and Australia, and more than 40 each in the UK, Canada, Japan and France.
Recruitment agencies contracted by the CCP are paid A$30,000 annually plus incentives for each successful recruitment.
They deal with individual researchers rather than institutions as it is easier to monitor them. Participants do not have to leave their current jobs to be involved in the plan.
This can raise conflicts of interest. In the US alone, 54 scientists have lost their jobs for failing to disclose this external funding, and more than 20 have been charged on espionage and fraud allegations.
In Australia, our education sector relies significantly on the export of education to Chinese students. Chinese nationals may be employed in various sectors including research institutions.
These nationals are targets for Thousand Talents Plan recruitment agents. Our government may not know what’s going on unless participants disclose information about their external employment or grants funded by the plan.
The case of Koala AI
Heng Tao Shen was recruited by the Thousand Talents Plan in 2014 while a professor at the University of Queensland. He became head of the School of Computer Science and Engineering at the University of Electronic Science and Technology of China and founded a company called Koala AI.
Members of Koala AI’s research team reportedly now include Thousand Talents Plan scholars at the University of NSW, University of Melbourne and the National University of Singapore. The plan allows participants to stay at their overseas base as long as they work in China for a few months of the year.
The company’s surveillance technology was used by authorities in Xinjiang, raising human rights issues. Shen, who relocated to China in 2017 but was as an honorary professor at the University of Queensland until September 2019, reportedly failed to disclose this information to his Australian university, going against university policy.
What should be done?
Most participants in the plan are not illegally engaged and have not breached the rules of their governments or institutions. With greater transparency and stricter adherence to the rules of foreign states and institutions, the plan could benefit both China and other nations.
The government can build partnership with other parties to monitor the CCP’s talent recruitment activities and increase transparency on funding in universities. Investigations of illegal behaviour related to the talent recruitment activity can be conducted by security agencies. Research institutes can tighten the integrity of grant recipients by disclosing any participation in the talent recruitment plans.
More resources should be invested towards compliance and enforcement in foreign funding processes, so that researchers understand involvement in the Thousand Talents Plan may carry national security risks.
Following US government scrutiny in 2018, Chinese government websites deleted online references to the plan and some Chinese universities stopped promoting it. The plan’s website also removed the names of participating scientists.
This shows a joint effort can influence the CCP and their recruitment stations to be more cautious in approaching candidates, and reduce the impact of this plan on local and domestic affairs.
Correction: This article has been updated to reflect the fact that Heng Tao Shen ceased to be an honorary professor at University of Queensland in September 2019.
In the early days of the COVID-19 lockdown in March, many temporary visa holders working in heavily casualised industries, such as hospitality and retail, lost their jobs and struggled to meet basic living expenses.
These included international students, backpackers, graduates, sponsored workers and refugees, among others.
Despite the devastating financial impact on these temporary migrants, the government excluded them from JobKeeper and JobSeeker. Instead, Prime Minister Scott Morrison said if they could not support themselves, it was time to go home.
Today, UnionsNSW is releasing the findings of a large-scale survey showing just how badly temporary migrants have suffered due to the lockdown and lack of financial support from the government. The survey of over 5,000 visa holders, conducted in late March and early April, paints a devastating picture:
65% of participants lost their job
39% did not have enough money to cover basic living expenses
43% were skipping meals on a regular basis
34% were already homeless, or anticipated imminent eviction because they could not pay rent.
For many, a worsening financial situation
Data from a separate new survey we are conducting confirms that the financial hardship of temporary migrants is likely to worsen in the coming months.
Through the UTS and UNSW-led Migrant Worker Justice Initiative, we conducted an online survey of over 6,000 temporary migrants in July. Preliminary analysis indicates that over half of the participants (57%) anticipated their financial situation would be somewhat or much worse within six months.
This does not take into account the impact of the stage 4 lockdown in Victoria, which came into effect in August after our survey.
Many respondents also said they could not “make their way home” when restrictions were being put in place to contain the virus — as Morrison had recommended — because flights were unavailable (20%) or unaffordable (27%). Others could not return because their country’s borders were closed (20%).
But for the majority, leaving Australia was not an option because of the great investment they said they had made in their studies (57%), their work and their futures in Australia (31%).
Half of our respondents also chose not to leave because they might not be able to return to Australia soon, or at all, and this was a risk they could not take.
The government’s treatment of temporary visa holders during the crisis also soured many on their experience here. According to our survey, 59% of international students and backpackers were now somewhat or far less likely to recommend Australia as a place for study or a working holiday.
One international student described his experience as
hopeless, lonely, wronged and without any support after five years paying my taxes and being part of the community.
And according to a backpacker,
the Australian government treated people on working holiday visas as consumable. If I go back to my country, I will never come to Australia again.
Calls for government support have been ignored
In early April, 43 leading academic experts across Australia warned of the severe humanitarian impact the lack of government support would have on visa holders who stayed in Australia.
As the level of destitution among temporary migrants became clear, charities tried to provide emergency food relief, and states introduced limited support schemes for international students, refugees and other groups of visa holders. Many universities, themselves facing significant financial challenges, also provided modest payments to international students.
Despite these interventions, hundreds of organisations — including unions, refugee service providers and migrant communities — raised the alarm in May, and again in July, about the worsening humanitarian crisis.
Still, the federal government continues to refuse support for temporary migrants, except for a small, one-off emergency payment provided to the Red Cross for a limited number of visa holders.
Australia is a global outlier in its callous treatment of temporary migrants during the pandemic. Other countries, such as the United Kingdom, New Zealand, Canada and Ireland, have all extended wage subsidies to temporary visa holders.
Advising temporary visa holders to go home does not diminish these obligations. Nor does it absolve Australia of its moral obligations to these people it encouraged to greatly invest in studying and working here.
It is unreasonable to expect international students to simply abandon their studies, or to expect other migrants to leave Australia when it has become their home. They have paid tax, contributed to our community and built long-term relationships.
Many of Australia’s low-wage industries are also reliant on migrant workers. In fact, during the lockdown, the government even changed the rules of student visas to permit them to work more hours in dangerous jobs in aged care, supermarkets, disability support and health care.
The government should also be concerned about the reputational damage to our international education market, and to the working holiday maker market, which provides a critical labour force for the horticulture industry.
Over the coming months, without ongoing government support, the living situations for hundreds of thousands of temporary visa holders in Australia will continue to deteriorate.
It is well past time the federal government acknowledge this crisis and focus its attention on meeting temporary migrants’ acute humanitarian needs.
Scientific publishing is not known for moving rapidly. In normal times, publishing new research can take months, if not years. Researchers prepare a first version of a paper on new findings and submit it to a journal, where it is often rejected, before being resubmitted to another journal, peer-reviewed, revised and, eventually, hopefully published.
All scientists are familiar with the process, but few love it or the time it takes. And even after all this effort – for which neither the authors, the peer reviewers, nor most journal editors, are paid – most research papers end up locked away behind expensive journal paywalls. They can only be read by those with access to funds or to institutions that can afford subscriptions.
What we can learn from SARS
The business-as-usual publishing process is poorly equipped to handle a fast-moving emergency. In the 2003 SARS outbreaks in Hong Kong and Toronto, for example, only 22% of the epidemiological studies on SARS were even submitted to journals during the outbreak. Worse, only 8% were accepted by journals and 7% published before the crisis was over.
Fortunately, SARS was contained in a few months, but perhaps it could have been contained even quicker with better sharing of research.
Fast-forward to the COVID-19 pandemic, and the situation could not be more different. A highly infectious virus spreading across the globe has made rapid sharing of research vital. In many ways, the publishing rulebook has been thrown out the window.
In this medical emergency, the first versions of papers (preprints) are being submitted onto preprint servers such as medRxiv and bioRxiv and made openly available within a day or two of submission. These preprints (now almost 7,000 papers on just these two sites) are being downloaded millions of times throughout the world.
However, exposing scientific content to the public before it has been peer-reviewed by experts increases the risk it will be misunderstood. Researchers need to engage with the public to improve understanding of how scientific knowledge evolves and to provide ways to question scientific information constructively.
Traditional journals have also changed their practices. Many have made research relating to the pandemic immediately available, although some have specified the content will be locked back up once the pandemic is over. For example, a website of freely available COVID-19 research set up by major publisher Elsevier states:
These permissions are granted for free by Elsevier for as long as the Elsevier COVID-19 resource centre remains active.
Publication at journals has also sped up, though it cannot compare with the phenomenal speed of preprint servers. Interestingly, it seems posting a preprint speeds up the peer-review process when the paper is ultimately submitted to a journal.
What else has changed in the pandemic? What has become clear is the power of aggregation of research. A notable initiative is the COVID-19 Open Research Dataset (CORD-19), a huge, freely available public dataset of research (now more than 130,000 articles) whose development was led by the US White House Office of Science and Technology Policy.
Researchers can not only read this research but also reuse it, which is essential to make the most of the research. The reuse is made possible by two specific technologies: permanent unique identifiers to keep track of research papers, and machine-readable conditions (licences) on the research papers, which specify how that research can be used and reused.
These are Creative Commons licences like those that cover projects such as Wikipedia and The Conversation, and they are vital for maximising reuse. Often the reading and reuse is done now at least in a first scan by machines, and research that is not marked as being available for use and reuse may not even be seen, let alone used.
What has also become important is the need to provide access to data behind the research papers. In a fast-moving field of research not every paper receives detailed scrutiny (especially of underlying data) before publication – but making the data available ensures claims can be validated.
If the data can’t be validated, the research should be treated with extreme caution – as happened to a swiftly retracted paper about the effects of hydroxychloroquine published by The Lancet in May.
While opening up research literature during the pandemic may seem to have happened virtually overnight, these changes have been decades in the making. There were systems and processes in place developed over many years that could be activated when the need arose.
The international licences were developed by the Creative Commons project, which began in 2001. Advocates have been challenging the dominance of commercial journal subscription models since the early 2000s, and open access journals and other publishing routes have been growing globally since then.
Even preprints are not new. Although more recently platforms for preprints have been growing across many disciplines, their origin is in physics back in 1991.
Lessons from the pandemic
So where does publishing go after the pandemic? As in many areas of our lives, there are some positives to take forward from what became a necessity in the pandemic.
The problem with publishing during the 2003 SARS emergency wasn’t the fault of the journals – the system was not in place then for mass, rapid open publishing. As an editor at The Lancet at the time, I vividly remember we simply could not publish or even meaningfully process every paper we received.
But now, almost 20 years later, the tools are in place and this pandemic has made a compelling case for open publishing. Though there are initiatives ongoing across the globe, there is still a lack of coordinated, long term, high-level commitment and investment, especially by governments, to support key open policies and infrastructure.
We are not out of this pandemic yet, and we know that there are even bigger challenges in the form of climate change around the corner. Making it the default that research is open so it can be built on is a crucial step to ensure we can address these problems collaboratively.
It was March 2020, and my plans to start a new cancer research project in Boston were called off for the same reason everything else was grinding to a halt: coronavirus. Facing indeterminate months confined to my sofa, I signed up to a call for scientist volunteers circulated by the University of Cambridge.
The requirements weren’t very specific, and after almost losing hope that I would ever hear back, I received a phone call inviting me to assist in the ramp-up of the UK’s testing capacity.
Three days later, at the end of March, I arrived with a handful of other volunteers at an industrial estate near the town of Milton Keynes, outside London.
Building a megalab
On the outside, the testing centre resembled a warehouse more than a lab, but an impressive management team including many of the UK’s leading scientists had already been assembled. The team leader, who had arrived the week before, introduced us to the task at hand: create a facility that would be the backbone of the UK’s testing strategy.
At this point, it seemed like a far-fetched idea to me. The “lighthouse” lab to process the bulk of the coronavirus test samples hadn’t even been constructed and unboxed equipment was piling up. There was no indication this would soon become the largest coronavirus testing site in the country.
From the start, one of the biggest challenges was in gathering equipment. Seemingly difficult tasks turned out to be straightforward, whilst trivial ones became surprisingly intractable.
Complicated, expensive machines donated from institutes all around the UK were installed within a couple of days; manufacturers massively ramped up production of sophisticated test reagents and we were able to build up our stocks.
But something as seemingly trivial as a shortage of pipettes threatened to stall the whole operation, as thousands of tests waited to be processed. In an emergency like this it was handy to have a direct line to institute heads around the UK who were eager to help. One more call and an army truck with dozens of pipettes and other equipment arrived within three hours.
In the end, the collaboration between permanent staff, scientists, external institutes, private companies and the armed forces made it possible to set up a working lab within a matter of days.
A motley crew of scientists
The volunteering scientists in my cohort were a diverse crew: most of us had PhDs and had spent years in scientific research, but we initially shared a common concern that few of us had experience dealing specifically with coronaviruses. My own expertise investigating the molecular causes of Parkinson’s disease and cancer seemed a far cry from viral diagnostics.
As it turned out, there was little cause for concern – the coronavirus test is actually quite straightforward. At its heart lies the Polymerase Chain Reaction (PCR) method, arguably one of the most widely used techniques in molecular biology labwork and a procedure undergraduates students learn as part of basic training.
In a PCR test, the genetic material of the virus is mixed with enzymes that can build and replicate viral DNA. Short DNA sequences called “primers” are then added. In a positive test the primers “recognise” viral genes and initialise their replication. Hence, when we see more DNA being produced, we know that it must belong to the Sars-CoV-2 virus, and the PCR test returns a positive result.
All of the newly arriving scientists had used the PCR technique in their own research many times before and it quickly became apparent that coordination and good management was a greater challenge than technical knowledge of coronavirus biology if this unprecedented undertaking was to succeed.
Every week, dozens of new volunteers were recruited from top universities and institutes all over the UK. Some of us stayed in pre-arranged hotels nearby, others commuted from our home towns. Each cohort received a week of intensive training and by the following week were themselves training the next intake of volunteers under the supervision of a shift leader.
Within two weeks, the site had changed beyond recognition. New labs had been fitted, robots had been installed, dozens of new hires were being trained every week and my initial worries started to dissipate. I began to think, “We can actually do this!”
With essential equipment installed, it was time to scale up. To an experienced scientist, performing a single PCR test is straightforward, but running tens of thousands of tests a day is a different story.
Time and again simple considerations turned out to be the most vital: “What’s the best way to extract the sample from its packaging?”, “Should the barcode be scanned before or after the sample is taken out?”, “At what moment should the pipette be mounted with a pipette tip?”
Feeding a robot with samples turned into a process with all the efficiency of a Formula 1 pit stop. One operator takes out the old samples, a second replenishes test reagents and a third loads another 94 samples – 10 seconds, done. Soon we had an integrated workflow of dozens of steps running in perfect orchestration.
While speed is important, precision is vital. A false negative result could see a nurse with COVID-19 going back into a care home to infect dozens of vulnerable patients; a false positive might see a healthy doctor sent home from ICU to self-isolate for a fortnight, or a key worker sending half their company into quarantine for no reason.
To prevent this, a sample must be tracked electronically and on paper at every stage. Every intervention by a scientist must be supervised by another to help prevent human error.
As our team grew, strict training routines needed to be established with clear rules. How do you write a “1”, an “I” and a “7”? Is this a “5” or an “S”? How do you distinguish an “O” from a “0”? Lecturing experienced professionals about how to write numbers and letters made me feel absurdly pedantic, but it quickly became clear that common rules have to be followed religiously to minimise all possible sources of error.
A month in, we had enough volunteers to work 24/7. I lost track of the time of day and the days of the week. The daily routine was governed by the mantra of Tedros Ghebreyesus, the head of the World Health Organization: “Test. Test. Test.”
Back in the first week, the manual sample handling process allowed a us to process a couple of hundred samples. With more volunteers coming in, this increased to a couple of thousand, and when we roped in robots to help, it quickly reached tens of thousands of processed tests per day.
Just like the spread of the virus we were competing against, our capacity was growing exponentially. What would normally have taken months or years to establish, now took days or weeks.
The eye of a political storm
The progress on testing has received a lot of bad press and many of us at the test centre felt we were being made personally responsible for hitting government targets. This added pressure caused frustration, especially when everyone gave their very best to make this undertaking a success.
We need to put things in perspective. From a starting point of zero, within weeks, the joint efforts of hundreds of volunteers allowed the lab to process more than 30,000 tests per day – or one test every three seconds.
This put us in a position where the processing of COVID-19 tests was no longer the limiting factor of the testing initiative and soon there has been hardly a day where our testing capacities were being used to the full. The debate now should be less about the available testing capacity and more on how to make best use of what is available.
The privilege of a lifetime
Most of the original crop of recruits have finished their time at the testing centre and have gone back to their labs to continue their previous research. What remains as one of the most positive takeaways from my perspective is that, despite the challenges and the country’s seeming divisions, it is still possible for us to rally around a common goal. Volunteers joined the testing initiative from all corners of the country, many of them from Europe and beyond living and working in the UK, eager to help out in the common effort to fend off the invisible enemy.
The work of these people has saved lives. It was my great privilege to have been part of this collaboration.
Every three seconds, someone in the world develops dementia. The most common form of dementia is Alzheimer’s disease. While researchers have identified a number of risk factors that are linked to dementia – including genetics, smoking, and high blood pressure – there is currently still no cure.
Part of the reason for this is because of how complicated it is to test potential Alzheimer’s drugs. In order to conduct clinical trials participants need to have symptoms. But by the time symptoms appear, it’s usually too late for treatments to have a large effect as many of their brain cells have already died.
But our latest research developed a new human cell model that is able to rapidly simulate the development of Alzheimer’s disease in the lab. This allowed us to identify a gene, called BACE2, that is naturally able to suppress the signs of Alzheimer’s disease in human brain cells. Our research is the result of around five years’ work, and was the collaborative effort of teams based in London, Singapore, Sweden and Croatia.
Researchers already know a lot about which genes cause Alzheimer’s disease or make someone more likely to develop it. These genes contribute to certain toxic proteins accumulating in the human brain. So our team thought that the opposite must also be true: our brain cells must also have proteins that can naturally slow down the development of Alzheimer’s.
One gene that can definitely cause Alzheimer’s disease is a gene found on the 21st pair of human chromosomes that is responsible for making the amyloid precursor protein (APP). Research shows that 100% of people born with just one extra copy of the APP gene (called “DupAPP”) will develop dementia by age 60.
People with Down’s syndrome are born with three copies of APP because they have a third 21st chromosome. But by age 60, only 60% of them will develop clinical dementia. We wanted to know why some people with Down’s syndrome have delayed development of – or never develop – Alzheimer’s dementia compared to those who have one extra DupAPP gene.
The simple answer for this is because they have an extra dose of all other genes located in chromosome 21. We believed that there could be some dose-sensitive genes on chromosome 21 that, when triplicated, protect against Alzheimer’s disease by counteracting the effects of the third APP gene.
These genes must then appear to delay the onset of clinical dementia in some people with Down’s syndrome by approximately 20 years. Studies have even shown that any future drug able to delay dementia onset by just five years would reduce the prevalence of Alzheimer’s in the general population by half.
To study the potential of the extra genes, we took hair follicle cells from people with Down’s syndrome and re-programmed the cells to become like stem cells. This allowed us to turn them into brain cells in a Petri dish.
We then grew them into 3D balls of cells that imitated the tissue of the grey matter (cortex) of the human brain. The 3D nature of the culturing allowed misfolded and toxic proteins to accumulate, which are crucial changes that lead to Alzheimer’s disease in the brain.
We found all three major signs of Alzheimer’s disease (plaque build-up in the brain, misfolded “tau” proteins and dying brain neurons) in cell cultures from 71% of people with Down’s syndrome who donated samples. This proportion was similar to the percentage of clinical dementia among adults with Down’s syndrome.
We were also able to use CRISPR – a technology that allows researchers to alter DNA sequences and modify a gene’s function – to reduce the number of BACE2 genes from three copies to two copies on chromosome 21. This was only done in cases where there were no indications of Alzheimer’s disease in our cellular model. Surprisingly, reducing the number of BACE2 genes on chromosome 21 provoked signs of the disease. This strongly suggest that having extra copies of a normal BACE2 gene could prevent Alzheimer’s.
The protective action of BACE2 reduces the levels of toxic amyloid proteins. This was verified in our cellular models, as well as in cerebrospinal fluid and post-mortem brain tissue from people with Down’s syndrome.
Our study provides proof that natural Alzheimer’s-preventing genes exist, and now we have a system to detect new potential protective genes. Importantly, recent research showed the protective action of BACE2 might also be relevant to people who don’t have Down’s syndrome.
Our results also show that all three signs of Alzheimer’s disease can be potentially detected in cells from live donors. Though this requires a lot more research, it means we may be able to develop tests that identify which people are at higher risk of Alzheimer’s disease by looking at their cells.
This would allow us to detect the disease before it starts developing in a person’s brain, and could make it possible to design personalised preventative treatments. However, we are still a long way from reaching this goal.
Most importantly, our work shows that all three signs of Alzheimer’s disease detected using our model could be prevented by drugs known to inhibit the production of the toxic amyloid protein – and this can be detected in as little as six weeks in the lab. We hope our discovery could lead to the development of new drugs aimed at delaying or preventing Alzheimer’s disease, before it causes brain cell death.
I estimate the gap in funding that needs to be filled to maintain our current research output at around $4.7 billion.
The funding foundations crumble
The timing of Dan Tehan’s higher education reform package could not have been worse for the university research sector.
The vulnerability created by universities’ reliance on international students has been brutally revealed this year. Travel bans prevent international students arriving in Australia and the COVID-19 recession undermines their capacity to pay tuition fees.
On 2018 enrolment numbers, revenue losses for universities for Commonwealth supported students would total around $750 million with this realignment. With only teaching costs funded, universities will have little or no surplus from their teaching to spend on research.
International student profits are larger than domestic – at around $4 billion. Much of this money is spent on research too, and much of this is at risk. The recession will also reduce how much industry partners and philanthropists can contribute to university research.
Australia’s Chief Scientist estimates 7,700 research jobs are at risk from COVID-19 factors alone. Unless the Commonwealth intervenes with a new research funding policy, its recent announcements will trigger further significant research job losses.
Combined teaching and research academic jobs will decline
Although less research employment will be available, the additional domestic students financed by redirecting research funding will generate teaching work.
But this reallocation between research and teaching will exacerbate a major structural problem in the academic labour market. Although most academics want teaching and research, or research-only roles, over the last 30 years Commonwealth teaching and research funding has separated.
After the latest Tehan reforms, funding for the two activities will be based on entirely different criteria and put on very different growth trajectories.
Academic prestige is attached to winning these grants, but the money allocated does not cover the project’s costs. Typically, universities pay the salaries of the lead researchers and general costs, such as laboratories and libraries.
Universities are partly compensated for those expenses through research block grants, which are awarded based on previous academic performance, including in winning competitive grants. But because block grants do not cover all competitive project grant costs, the system has relied on discretionary revenue, much of it from students, to work. It will need a major rethink if teaching becomes much less profitable.
The stakes are high
University spending on research (which was over $12 billion in 2018), has nearly tripled since 2000 in real terms.
Direct government spending on research increased this century, but not by nearly enough to finance this huge expansion in outlays. In 2018, the Commonwealth government’s main research funding programs contributed A$3.7 billion.
An additional $600 million came from other Commonwealth sources such as government department contracts for specific pieces of research.
These research-specific sources still leave billions of dollars in research spending without a clear source of finance. Universities have investment earnings, profits on commercial operations and other revenue sources they can invest in research.
One clue is in the name. Pre-prints are versions of research papers available before they are formally published.
The term has been around for decades. In pre-internet days, physicists posted each other photocopied versions of draft papers for comment.
Once the internet came along, it was clearly more efficient to put these papers in a central location. In 1991 the very first electronic pre-print server was born, now called arXiv (pronounced “archive”).
This meant anyone with access to the internet could read and comment on the work. That pre-print server now holds almost 1.7 million papers.
Not surprisingly, the number of pre-prints published on these servers has also grown exponentially. And pre-prints specifically relating to COVID-19 have increased the numbers further.
So, what’s the problem? Isn’t it good that all this research is being made available? Well, yes and no.
Researchers need to share their coronavirus work quickly
In a rapidly changing environment such as a pandemic, it is important researchers know what kind of work is happening and who is doing it. Pre-prints allow them to find out quickly.
Researchers, who are the intended audience for these pre-prints, understand there can be a major difference between a pre-print and the final published version.
The public, including journalists, can also access these pre-prints as they’re openly available.
That’s very different to the vast majority of academic publications, which are held behind paywalls, with charges for a single viewing in the tens and sometimes hundreds of dollars for people without a subscription.
But the public, including journalists, is generally less aware of the provisional nature of the research commonly found on these pre-print servers.
This situation, with the media publishing items based on unproven information, has become so problematic that Australia’s chief scientist is urging the public to be wary of claims of breakthroughs.
Pre-print servers themselves already point out the articles have not been peer reviewed and should not “be reported in news media as established information”, as seen in the yellow box below.
The path to publication
Once a research project has discovered something, the research group will write it up as a paper which describes what they did, what they found and what makes this a new finding.
This paper is sometimes published as a pre-print. The paper is then submitted to a journal for consideration and the journal editors send it out to experts in the field to comment on the work – a process called peer review.
The reviewers send back their comments, which might request the authors add extra information to the paper, or sometimes do additional experiments. The researchers address these comments and resubmit the paper before it is published.
This can take a long time, from months to sometimes years before the paper is actually published. In the middle of a pandemic that’s a problem.
The academic publishing industry is trying to improve the flow of information. Many publishers are making COVID-19 related articles openly available.
Many publishers are also fast-tracking peer review. But even with this sped-up timeframe, the process still takes a while. Pre-prints are fast.
The thing to remember with pre-prints is they have not been peer reviewed. While many publications don’t change a great deal after peer review, some articles require considerable amendment or even withdrawal.
All of this doesn’t mean that what you read in a pre-print is rubbish. Actually, pre-prints are an important part of the publication process.
When looking for information, ideally use published research – formatting and publisher logos are clues. But if you want to decide whether a pre-print contains valid information, try finding another article making similar claims.
So what happened with the blood type research? The original pre-print, published on March 16, had multiple comments. On March 27, a second version was uploaded, which emphasises “this is an early study with limitations”.
The system works, as long as you know what you are looking at.