Tuberculosis was the great killer in Ireland for much of the first half of the 20th century. In 1922, the year the Irish Free State came into being, 4,614 people died from TB. Some 611 of them were children below the age of 15.
It was the silent terror that haunted the country right up until the 1950s when visionary health minister Noël Browne introduced mass free screening for TB and initiated a huge construction programme of hospitals and sanatoria.
But, there was another tool in the war against TB that was already having a significant impact by the time Browne took office: a vaccine called Bacillus Calmette-Guérin (BCG).
It had been first been licensed in the US in 1921 and was finally introduced to Ireland in 1937. It was given to infant children as a TB prevention and it worked. Tuberculosis, which many had feared would never be brought under control, was effectively a historic footnote here by the end of the 1960s.
Irish children continued to receive the BCG shot until 2015. A global shortage of the vaccine means children below the age of five have not received it, although stocks are said to be growing once more.
Almost 100 years after it was first developed, BCG is in the news once again - and for a very different reason. Covid-19 may have little in common with TB, but it appears that those who took part in the long-running BCG programme are experiencing a far lower fatality rate from the coronavirus than those that did not.
And Irish doctors are leading the way in the research. A study of 178 countries by an Irish medical consultant working with epidemiologists at the University of Texas shows countries with vaccination programmes - including Ireland - have up to 10 times fewer coronavirus cases, compared to those where BCG has not been administered.
This translates into a death rate that is significantly less, according to urologist Paul Hegarty of Dublin's Mater Hospital. "We did not expect to see such a marked difference," he said this week. "Over the 15 days [of the study], incidence of Covid-19 was 38 per million in countries with BCG vaccination whereas the incidence of Covid-19 was 358 per million in the absence of such a programme. The death rate was 4.28 per million in countries with BCG programmes and 40 per million in countries without such a programme."
One of the country's leading immunologists, Professor Luke O'Neill, says if the connection to BCG is proven, most of the country would have immunity to Covid-19. This "potential game-changer," he says, is "feasible and should be considered" but "it doesn't mean we change behaviour such as physical distancing and washing your hands".
Right now, there are medical teams all over Ireland - and the world - who are working to find a solution to a crisis that has been described by the United Nations as the greatest to face the globe since World War II.
An indication of the huge amount of work being conducted around the world was apparent on Thursday when Prof O'Neill tweeted that "267 Covid-19 remedies are now in development".
He accompanied his tweet with an infographic depicting 301 ongoing clinical trials, including several in Ireland.
THE IMMUNE RESPONSE
One of those is run by Professor Cliona O'Farrelly from the School of Immunology and Biochemistry, Trinity College Dublin.
Like many experts, she is keen to uncover why it is that Covid-19 affects some patients far worse than others - research in both Iceland and China, for instance, show that more than half of all of those infected with the virus, according to random testing, display no symptoms at all, while others get severely ill and a small minority die.
Now, in conjunction with St James's Hospital in Dublin, Prof O'Farrelly is leading a team that is hoping to get answers quickly - with the help of patients with Covid-19 that are admitted to the hospital.
Thanks to blood and nasal samples gathered from each patient presenting to the hospital with the virus, her team can look "for markers of the patients who will have a catastrophic response to infection and markers of those who will have a quick, effective and protective immune response".
Prof O'Farrelly says there is a realisation that a lot of people who get infected do not get that sick and "it is something to do with their immune system. We are trying to find what is different about immune systems of people who have catastrophic responses".
Already, preliminary results are showing that patients who require ventilation have altered immune cells and raised levels of some immune proteins in their blood.
"It would be really useful," Prof O'Farrelly says, "if we can identify which patients will not have a catastrophic response because then they can be sent home quicker and free up hospital beds for those who become dangerously ill.
"And it is really important for us to find out if people can become immune to the virus, to show that if they make antibodies that they won't become infected again. And also to discover how many people are immune to the virus.
"There's so much we don't know," she adds. "The virus has only existed in humans for six months."
Meanwhile, at Queen's University Belfast, Professor Danny McAuley is leading a UK-wide clinical trial, offering an innovative cell therapy treatment for Covid-19 patients with acute respiratory failure.
Prof McAuley is investigating the use of allogeneic Mesenchymal stem cells (MSCs) in patients with a complication known as Acute Respiratory Distress Syndrome (ARDS) caused by Covid-19. Many of those who go on to die from complications arising from the virus develop ARDS, where the lungs become leaky and inflamed and filled with fluid. Ultimately, it can lead to respiratory failure necessitating admission to an intensive care unit and respiratory machines. But with MSCs, inflammation can be reduced, infection fought and injured tissue repaired.
A NEW VACCINE AND ANTI-VIRALS
Ultimately, however, there is a growing sense that the only way that the pandemic can be brought under control and normal life resume is with the development of a vaccine.
That's the view of Dr Anthony Fauci, the US leading immunologist and the country's public face in the fight against the virus. Earlier this week, he insisted that 'normality' could not be restored until a vaccine and been developed and widely distributed.
"If 'back to normal' means acting like there never was a coronavirus problem, I don't think that's going to happen until we do have a situation where you can completely protect the population," he insisted.
"I believe that with the therapies that will be coming online, and the fact that I feel confident that over a period of time we will get a good vaccine, that we will never have to get back to where we are right now."
Irish microbiologist and evolutionary biologist James McInerney of the University of Nottingham says bringing this crisis to an end will be fiendishly difficult. "There are three possible ends to it," he says. "One is the idea that the virus infects so many people that you have herd immunity and a significant proportion of the population would be either infected by the virus or in the fullness of time we'd have a vaccine.
"And both of those are in the long run. Ultimately, humans have to become immune to it.
"The second thing, especially in the absence of a vaccine, is the development of drugs where if people have the virus, it doesn't become a killer. You've seen things like HIV. It used to be a death sentence but now people can live with HIV. Perhaps we won't develop strong immunity to the coronavirus and it's not proven yet that we will develop strong immunity, we will need drugs [anti-virals] to help us along when we get infected."
THE SIMPLE TEST SOLUTION
Another aspect in the fight to bring Covid-19 under control is technology, McInerney says.
"Dipstick-type technology - something like the pregnancy test. It might be the case that a blood [sample] is needed so it might be something that's not too dissimilar from what diabetics use.
"Or you could imagine a technology where you can effectively brush your teeth and it tells you if you are okay or not to go into work today. Basically a test that wouldn't be terribly invasive. If they could be developed cheaply and widely distributed, they really could have a significant effect. Society could function, but as long as everyone tested themselves.
"In January, that was a fantasy. But today it's not so much of a fantasy any more. But right now, we can't magic up a situation where everyone is going to be immune or where a vaccine can suddenly arrive."
CONTACT TRACING APPS
A different sort of technology is proving vital in keeping the number of infections down in several countries, including South Korea and Singapore: so-called contact tracing apps.
Numerous mobile apps are being developed that use proximity or location data to notify someone who has recently been near an infected person, so that they can then take preventive action such as self-isolating.
In the UK, a government-backed project - which users would opt into - is under way and could be launched within weeks, while the US is likely to introduce several such projects across multiple states.
While these digital pandemic-fighting initiatives could be pivotal in helping to contain Covid-19, there are still numerous hurdles. A primary task will be garnering high enough levels of adoption.
According to Oxford University researchers, at least 60pc of the target population would need to use the technology for it to be effective. In effect, that would involve carrying their phones with them at all times, even when exercising. In Ireland, a HSE contact tracing app is expected to be unveiled next week. The app will employ short-distance Bluetooth to signal where users are near to each other and record this information. If a person is confirmed to test positive for Covid-19, the disease caused by the coronavirus, everyone who came within close contact of them for a prolonged period of time will be notified.
The app will be opt-in, according to the HSE's head of communications Paul Connors, but will have additional features such as being able to report on your well-being, which will be fed back to the HSE for future tracking of the spread of the virus.
Users' privacy must be protected in a way that adheres to existing regulations and maintains public support. There are growing concerns that the crisis is being used by governments in countries such as China to usher in mass surveillance.
"We are no longer in the initial stage of Covid spread, and Ireland is already under general restrictions," said Elizabeth Farries, technology and human rights specialist at the Irish Council for Civil Liberties last week.
"How will the app further contribute to efforts already in place? How will it result in different behaviours from people who have signed up? Can the app coherently or meaningfully contribute to containing Covid, so that its deployment is worthwhile?"
And Antoin Ó Lachtnáin, who is director of Digital Rights Ireland, an organisation that defend people's civil, human and legal rights on digital issues, notes that while an emergency may demand allowing data usage in ways that would not otherwise be acceptable, a clear process exists for validating that such an app complies with privacy requirements, including a legally required Data Protection Impact Assessment.
"One thing is certain," says James McInerney. "There are no easy solutions.
"We are in an unprecedented time and we're up against the clock.
"Right now, you have over 1.5 million diagnosed with the virus around the world. We all saw how quickly that happened. Nobody can get complacent."