As we’re faced with lockdown orders, social distancing, and a devastating pandemic, it’s hard to believe the human immune system is successful. But, then again, we’re successfully fending off swarms of pathogens every single day, so we probably also shouldn’t be too rough on our immune systems.

In the end, it’s all a matter of how you look at things, says Nobel Laureate Sir Gregory P. Winter.

Sir Winter was awarded the Nobel Prize for his work on the therapeutic use of monoclonal antibodies, and he was joined in conversation by two other Laureates: Bruce A. Beutler and Jules A. Hoffmann, who were awarded the prize for their work on innate immunity.

Innate immunity is one of the two main types of immunity. It is the oldest evolutionary defense strategy, emerging some 500 million years ago. Humans aren’t the only ones who have it, it’s also the dominant immune response in plants, fungi, insects, and some primitive multicellular organisms. The other response is called the Adaptive immune system, a system of specialized, systemic cells and processes that eliminates pathogens.

“Adaptive immunity is based on an additional tier of cells, lymphocytes, and in both cases, the cells make a repertoire of T cells or antibodies of diverse structures.”

The conversation between the three laureates took place at the Science Days Lindau Nobel Laureate Meetings, where Nobel Laureates meet with young researchers from all around the world. Except this year, the whole meeting had to be carried out online, instead of in Lindau, Germany.

At one point, the Laureates’ conversation switched to a topic we don’t think about too often: just how good is our immune system?

“I would start with the point of view that it’s not very successful,” Beutler comments. “It has allowed us to survive in an evolutionary sense but not very well. We know from our species that if they live in the wild they don’t live very long — and it’s because of infectious disease.”

This is not something that we consider acceptable in our advanced society, Beutler notes. Without vaccines or without the help of antimicrobials, we wouldn’t be able to enjoy the lifestyle we’ve grown so accustomed to, and those only came very recently in our evolutionary history.

But for Hoffman, that’s not the whole story.

“I have the impression that when we travel, we meet so many microbes when we shake hands and so on, and we come back to our home without having picked up anything. So this is probably due to innate immunity, but there must be fantastic protection.”

“Out of the millions of bacteria, only about 100 species are a problem for humans, and the same is for the number of fungi for humans. Only 20-30 fungi out of millions of species. The same is even true for viruses, so I would argue that the immune system is a very efficient system of protection, unless we are immunocompromised or we live in a society biased towards infection, such as Wuhan probably was.”

This brings up an important point that also relates to the current pandemic. In much of the ‘western’ developed world, infectious diseases have largely been kept under control in the past few decades — up to the point that we’ve almost forgotten how to deal with them. It’s perhaps not surprising that Western Europe and the US fared so poorly: for the past 50 years, we’ve focused way more on chronic than on infectious diseases.

Meanwhile, for much of the world, infectious diseases are a major day-to-day threat. The fact that infectious diseases have fallen into the background only for a part of the population, and only in the past few decades, seems to indicate that we weren’t really doing that good of a job beforehand.

For Sir Winter, it’s a matter of perspective. It depends on how you look at things, he argues. We may be vulnerable to some pathogens, but for the most part, we keep microbes at bay.

“I tend to think we’ve been rather successful, based on absolute standards. If you’d take a group of cells and incubate it at 37 degrees, it wouldn’t take long before it’s taken over by fungus [or] bacteria. I think we also do pretty well in combating the fact that these viruses are constantly changing, and yet our immune system keeps up.”

I guess it depends whether you’re glass half empty or glass half full, depends where you stand.”

This debate may be a bit more than just a philosophical one. The coronavirus pandemic has shown us that we may need to think about our relationship with infectious disease, especially with zoonotic diseases (that emerge in animals).

Both wildlife trading and agricultural practices have intensified in the past two decades, and both represent potential reservoirs of diseases.

Whether or not you think our immune system is doing a good job, we are still vulnerable to pathogens — especially ones that migrate from another species. It doesn’t take too many of them, either.

An international report from 2012, for example, states that a total of 56 such diseases were responsible for 2.5 billion cases of illness and 2.7 million deaths across the globe each year. Meanwhile, flu-like viruses have wreaked havoc in the past century, with the Spanish flu causing 50 million deaths in 1918, and the Hong Kong flu caused 700,000 deaths in 1968. Who knows how high the counter will be for the current pandemic.

We need to stop what drives mass epidemics rather than just respond to them. We are nearing a precipice where, without substantial societal change, COVID-19 will be one of several devastating diseases of the 21st century.

Unfortunately, we are living in the age of the pandemics, and alone, our immune systems just can’t cope with that.