Science is a process

For the past 12 weeks, in discussions about the current coronavirus crisis, we have all heard a lot of talk about “science.” These discussions miss the point. Science is not a thing, it’s a process.

When physicians and scientists discuss science, we are talking about process. Someone makes a statement or proposes a theory about the world around them. We then test this theory against the observations that we see in the clinic, or against experiments that we do in the laboratory. If the theory explains the observations or the experiments, we perhaps accept it. If it does not, we alter the theory and make another set of clinical observations or perform another laboratory experiment to test it again. It is this testing and doing that make up science.

The current theory in vogue states that the virus is the same everywhere. It is highly transmissible, we all have the same susceptibility to it, and that only social distancing and a vaccine will protect us going forward. These theories are not new. In fact, they are very old.

Quarantine for infectious illness has been performed for millennia. The word “quarantine” comes from the Italian word “quarantino,” when arrivals to the island city of Venice from areas affected by the bubonic plague in the 14th century were isolated for 40 days.

Vaccination also has a long history. It was called “variolation” against smallpox and was practiced since antiquity. It had a revival in Georgian England in the early 1700s and, in 1797, Edward Jenner demonstrated that cowpox vaccination could prevent smallpox.

In the 21st century, advances in immunology and molecular biology have expanded our understanding of the world dramatically. This allows us to propose other theories for what is happening in the COVID-19 pandemic. For example, my colleagues and I have proposed a theory that the coronavirus infects a master cell that controls the immune system called the dendritic cell. It does this through binding not only to the ACE2 receptor everyone knows about, but also to a co-receptor called DC-SIGN. This ancient receptor binds to viruses with a lot of sugar molecules on the proteins that make up their coat.

Why do we think this is the case? A lot of viruses act in this way, such as HIV in AIDS and the virus that causes SARS, the disease closest to COVID-19.

When infected in this manner, the immune system initially gets confused. This results in many of the observations we see with this disease, such as a poor initial immune response with loss of white cells called lymphocytes. As the immune system recovers it can overcompensate with cytokine storm.

This theory makes a number of predictions.

First, we know that dendritic cells don’t function as well as you get older, if you have diabetes or if you have certain immunodeficiencies. These appear to be several of the risk factors for COVID-19. There is also genetic variation in the proteins that make up the immune system which can possibly account for variations in severity of infection.

Second, compounds that alter the function of this dendritic cell should modulate the severity of infection. Vitamin D3, zinc and certain H2 blockers like famotidine, all of which modulate the dendritic cell, appear in early studies to be associated with clinical benefit. Other drugs currently in clinical trials also affect the dendritic cell and could be expected to have clinical benefit as well.

Finally, it is well known with other human viruses that a virus generally gets weaker over time. This means that infections later in pandemics usually result in less severe disease and fewer deaths. In 2020, we can examine mutations in the coronavirus over time and see which mutations become more frequent. If this theory is correct, then mutations predicted to make the virus weaker should become more common as the pandemic progresses. This indeed may be the case.

Competing theories therefore exist to explain what is happening with the COVID-19 pandemic. There are many more than just these two. It is unclear which theory is correct. However, it is the job of science — the process, not the thing — to test these theories against clinical observation and laboratory experiment to see which one fits best.

Dr. Adam Brufsky is a professor of medicine and associate chief of the division of hematology-oncology at the University of Pittsburgh School of Medicine. These opinions are his own and not necessarily those of the University of Pittsburgh or the University of Pittsburgh Medical Center.