Ashley Hanson

Why is There no Cure for the Common Cold? Photo by​ ​Brittany Colette​ on​ ​Unsplash The common cold has the unique distinction of being one of the most elusive infectious diseases in the world, as well as one of the most widespread. Try to think of one other infectious disease that inspires such a high level of resignation. The common cold winds its way through schools and homes, cities and towns to make people absolutely miserable for a few days. Most people don’t give it a lot of thought; it just is. Adults typically have two to four colds a year, and we’ve come to grudgingly accept this as a part of life. As for the public; their understanding is a unique mix of false assumptions and folklore. In 1984, the University of Wisconsin-Madison ran an experiment to investigate whether or not one of one of the most popular ways of catching a cold was true or not. In the test, 16 volunteers got willingly infected with the cold virus, and they then kissed 16 healthy test subjects for a minute. The result? Only one healthy person got sick. The most common ways people believe to be a cure for the cold have turned out to be false. However, this has done little do discourage odd remedies. Then-president Calvin Coolidge sat it an airtight chamber. This chamber was then filled with a noxious, pungent gas for almost 60 minutes. His doctors swore breathing this concoction in deeply would banish his cold. Spoiler alert, it didn’t. So-called “winter remedy” sales in the United Kingdom reach around £300 million each year, despite the fact that most over the counter products have little to no influence on your symptoms. Some do contain an analgesic called paracetamol, but the dosage is too low. Dosing yourself with vitamin C has little impact. Hot toddies, immune system “boosts,” and medicated tissues are highly ineffective. Antibiotics do absolutely nothing for the common cold. The only failsafe you have is to quarantine yourself away from humanity for the rest of your life. Modern science changed the way we, as a society, practiced medicine in almost every different field, but it has yet to come up with a radically effective treatment for this infectious disease. The problem is that almost all colds feel the same. However, the only common feature they all have is that the viruses that cause them have adapted to be able to damage and enter your cells in your respiratory tract. Otherwise, the viruses all have different organism categories, and every one has a different way of invading cells. This makes formulating a catch-all treatment almost impossible. Today, scientists identified seven different virus families that are behind most colds, including adenovirus, coronavirus, influenza and parainfluenza virus, metapneumovirus, respiratory syncytial virus (RSV), and rhinovirus. Each category has a host of subcategories called serotypes. There are around 200 of these. Rhinovirus is the smallest but most prevalent. It causes up to 3/4ths of all cold infections in adults. To put an end to the cold, we have to take on all of these different virus families at some point. The first attempt to make a rhinovirus vaccine came from scientists in 1950. They used the method Louis Pasteur pioneered by introducing a microscopic amount of the rhinovirus to the host via injection. This exposure prompts your body’s immune system to recognize and fight off the virus to prevent a second infection. However, those people who got the vaccine got sick with the common cold just as easily as people who didn’t get it. The next 10 years saw the techniques scientists used for isolating the cold virus get refined. This proved that there were different types of rhinoviruses, and scientists came to the conclusion that it wasn’t possible to make a vaccine for the rhinovirus the traditional way. Trying to produce dozens of vaccines for each strain of rhinovirus is impractical, and the final human trial happened in 1975. The Expert Review of Vaccines put out an editorial in early 2016 that brought about the hope for a rhinovirus vaccine. These scientist’s motivation was the knowledge that because we now have vaccines against several dangerous viruses like cholera, influenza, measles, yellow fever, and polio, it was time to try diseases that people get sick more often with things like the common cold. The first attempt at the rhinovirus vaccine was in 1953. Winston Price was an epidemiologist who worked at Johns Hopkins University. While he was working, nurses working in his department started showing signs of being sick with a sore throat, cough, mild fever, and runny noses. He took nasal cultures of each infected nurse, and he grew the virus. The result was too little to be influenza. In 1957, he published a paper where he named this new virus the JH Virus. Using a small amount of dead rhinovirus, he tried to create a vaccine. When your immune system detects a virus, no matter if it’s alive, dead, or weakened, it tries to destroy it. Antibodies stay in our system for a long time after the virus is gone. If you get sick with the same virus, the antibodies will recognize it and start attacking it before it can take hold. At first, William was hopeful. He gave volunteers the JH virus vaccine, and he found that, on average, these people had 8 times fewer colds. He believed he cracked the code, but it was short-lived. His vaccine did work well against that particular strain. However, other trials showed the vaccine to be ineffective. This led him to believe there were multiple strains of the rhinovirus. By the time the late 1960s came around, there were dozens of rhinoviruses. The University of Virginia’s science department decided to go a different route. Instead of giving test subjects a single rhinovirus strain, they would combine 10. But, this failed to protect the participants from an infection. Hope for creating a vaccine dimmed, and researchers looked for other ways to combat the cold. Between 1946 and 1990, almost all respiratory virus research in the United Kingdom was done by the Common Cold Unit. This was an entity found in a former military hospital near Salisbury and backed by the Medical Research Council. In over 40 years, over 20,000 people volunteered to get infected with the rhinovirus in hopes of finding a cure. They switched their focus to cold treatment, starting in the 1960s and 1970s. Research into a protein your cells secrete called interferons was just gaining momentum. These are messengers that let cells know there is a virus invading your system. In response, the cells start producing an antiviral protein. This protein is instrumental in stopping the ability of the virus to spread. Researchers decided to see if they could use interferons to treat colds. 32 volunteers got infected, and then the researchers gave them a nasal spray containing either a placebo or an interferon. 16 volunteers got a placebo, and 13 got sick. 16 volunteers got the interferon, and only 3 got sick. This kicked off a mad rush of interferon research, but they discovered a huge stumbling block. The interferon only worked if a person got them at the exact same time they got the rhinovirus. While you can recreate this in a lab, you don’t start seeing symptoms of a cold outside of a lab until 48 hours after the initial infection. It’s too late by this point. By the time the 1990s came around, much research had made a shift to Aids and HIV, and research into a cure for the cold fell to the wayside. In Paddington, West London sits the Imperial College’s St Mary’s Hospital. On the third floor, you’ll find the asthma specialist and professor of respiratory medicine, Sebastian Johnston. In 1989, he was a PhD student who went to the CCU right before it closed to study their various methods of detecting viruses. He developed a polymerase chain reaction for his PhD on asthma. This reaction magnifies your DNA so you can have an easier time identifying viruses. He found that viruses were the cause of a significant instance of children’s asthma attacks, and rhinovirus made of 50% of the virus content. It wasn’t until the 1990s came around that scientists understood exactly what they were up against. Electron microscopy had come far enough to allow them to see an organism up close and personal. In spite of the fact that the common cold is a virus that is terrifying good at infecting us through the nasal passages, they’re very simple. At the core, the rhinovirus is strands of RNA encased by a shell. Rhinovirus is almost exactly the same on the inside, tiny pattern alterations on the outer shell trick your immune system into thinking they’re all different. This is why Winston Price’s vaccine didn’t work. Originally, scientists widely believed that there were around 100 strains that they put into A and B families. However, they discovered a new virus cache in 2007 that brought the total up to 160 and led to the creation of family C. Dr Johnston contacted Jeffery Almond in 2003. Dr Almond was a former Reading University virology professor who recently took a position at Sanofi as the head of vaccine development. At this time, Sanofi was creating a vaccine for influenza, and they set their sights on conquering the common cold. For medical professionals, a vaccine is the preferred way to treat patients over drugs because vaccines are great at shielding their host from any invasive organisms before said organisms can cause damage. Drugs get taken over long periods and vaccines are a single injection. ​People also want cheap vaccines. Dr Almond thought that there could be a case for commercial production of the rhinovirus vaccine. Rhinovirus puts a huge burden on the health system through secondary infections that require more treatment, days off work and school, and potential hospitalization. Dr Almond was able to convince the company he worked for that it would be financially viable to create a rhinovirus vaccine. Drs Almond and Johnson got to work reviewing the approaches scientists took in the 1960s and 1970s. They quickly discarded the idea of creating a mega vaccine that had all of the 160 rhinovirus strains on the account that it would be too expensive, complex, and heavy. They started to wonder if all of the virus strains had a structure that was conserved or identical. If there was, they could create a subunit vaccine. This approach had success with HPV and hepatitis B. They started comparing different rhinovirus serotypes and looking at each genetic sequence. They found one specific protein that the shell seemed to have across dozens of the serotypes. They took a small piece of rhinovirus 16’s shell and mixed it with a stimulus that mimics the signal your body uses to trigger an immune response when it detects a virus. Then they injected it into mice. They hoped that the mice’s immune system would recognize the shell protein as an invader, and this would confer immunity to the whole family. Scientists mixed rhinovirus serotype 1, 14, and 29 with immunized mouse blood in Petri dishes. They expected to see an immune response to 1 because its genetic sequence was almost a carbon copy of 16. Serotypes 14 and 29 were different. However, the white blood cells responded favorably to all three. They got a group of respiratory medicine specialists together to go over their findings. They all agreed that the results looked good so far. However, just when it seemed like a cure was in reach, Sanofi changed directions and pulled funding. Sanofi’s new management team gave the Imperial College the patent protecting the idea of a cold vaccine back in 2013. However, Imperial College didn’t have the funding needed to further the vaccine development process. This was immensely frustrating to Dr Johnston, but he couldn’t do much about it. Imperial started to look for new backers. At the same time, a pediatrician at Atlanta’s Emory University named Martin Moore started working on a competitive approach to the exact same issue. As a children’s respiratory disease specialist, he presented a straightforward solution that had his colleagues struggling to accept it. He started looking at the research from the 1960s and 1970s. He saw that scientists showed that they could take a single rhinovirus strain, kill it, put it in a vaccine, inject it, and protect people against that strain. Moore wondered why you simply couldn’t make a vaccine that had all of the rhinovirus strains mixed together. The problem was with logistics, not science. The National Institutes of Health gave Moore funding, and he went to the American Type Culture Collection and Centers for Disease Control to apply for samples of the rhinovirus’s serotypes. He decided that using 50 strains instead of the full 160 would support his theory. He developed a vaccine that had 50 serotypes, and he tested it out on rhesus macaque monkeys. He then mixed their blood with viruses and found that they had a very strong antibody response to 49 serotypes out of the 50. However, it wasn’t possible to see if this would protect the monkeys themselves from the cold because human rhinoviruses don’t work on monkeys. The vaccine still has a long way to go before human trials. For one, it has to follow conditions set under good manufacturing practice (GMP). These are regulations companies are required to follow for licensing purposes. They specify that any substance has to stay separate to reduce the possibility of cross-contamination. This is a challenge, especially for a vaccine that contains 160 serotypes. The biggest number of serotypes currently in a single vaccine is the pneumonia vaccine with 23. Moore is looking toward the polio vaccine for a manufacturing model since the rhinovirus and polio are related biologically. The production scale would be significantly larger. Moore’s startup got a $225,000 grant from the National Institutes of Health to create his rhinovirus vaccine. Currently, one of the biggest barriers to finding a cure for the common cold lies in the commercial sector. University researchers can only do so much, and many grants max out at around $2 million. Pharmaceutical companies get the burden of carrying out vaccine development. To date, success is a very rare creature, while flat out fails have been spectacular. Novavax, a United States’ firm saw shares fall by a whopping​ ​83%​ after they developed a vaccine for RSV that failed late-stage clinical trials. RSV is less common than rhinovirus, but it can easily cause death or great harm to the elderly, infants, and anyone with weakened immunity. Novovax’s failure is exactly why pharmaceutical companies are leery. Vaccines are 5% of the overall market in the pharmaceutical sector, and there are only a handful of giant companies developing them including AstraZeneca, Johnson & Johnson, GlaxoSmithKline, Merck, Sanofi Pasteur, and Pfizer. After these companies spend an estimated $1 billion for vaccine development, distribution and manufacturing costs come in. There has to be a viable return on the company’s investment. If not, you’re essentially wasting the company’s money. ​Do that a few times, and you get bankruptcy. Research into a rhinovirus vaccine started again in October of this year after Sebastian Johnston got funding from Apollo Therapeutics. This is a newer pharmaceutical company backed by Johnson & Johnson, GSK, and AstraZeneca. Dr Johnston believes if this vaccine can effectively protect people against 20 serotypes of the rhinovirus, there’s a good chance it’ll work against all of them. It’s estimated research will take around 18 months before it heads to the clinical trial phase. Should it make it through clinical trials, it’ll have to have regulatory approval. Then, the vaccine would go to high-risk groups like people with asthma, COPD, or the elderly before going to the rest of the population. Eventually, rhinovirus would cease to circulate because the majority of the population has the vaccination. This is​ ​herd immunity​. However, this is still way off in the future as of today. Around 80% of all vaccines or drugs that make it to the clinical trial level because experimentation on mice was successful fail in human tests. But there are now large pharmaceutical companies that have programs for the rhinovirus vaccine development. There are also smaller researchers all working toward a common goal of curing the common cold. People are starting to think that a cure may actually be possible.