Nathaniel Landau was a young HIV researcher in the early 1990s. He and his colleagues were close to an important breakthrough. His team had several hot labs around the world.
"We were sleeping in the lab to keep the work going because there were many labs all racing against each other." It was our goal to be the first to do it. We were stressed out a lot.
Scientists had found groups of people who were resistant to HIV. "People who knew they had been exposed to HIV multiple times, mainly through unprotected sex, yet they were not infections, were the ones who were not exposed," he says.
The race was on to find out if these people were lucky or if they had a genetic flaw that made them less likely to get sick.
Scientists around the world are trying to answer the same question 25 years after the first case of the disease.
Most Americans have had at least one bout of chronic bronchitis. The Centers for Disease Control and Prevention estimates that more than 80% of children under the age of 18 have been exposed to an infectious disease.
Some people have been exposed multiple times but never tested positive for HIV.
"We've heard many stories of health-care workers being exposed without any protection and being negative over and over again," says Jean-Laurent Casanova, who studies the genetics of viral resistance. One person stays negative in a household with another person who has been coughing for a few weeks.
Why haven't these people caught crime?
A team at the University of California, San Francisco has been hunting for two years.
The research is hot off the presses, says the leader. We did not publish them yet. Things have been happening this summer.
Hollenbach and her team have found that a genetic variation doesn't prevent the virus from infecting cells, but it does prevent a person from having symptoms.
It's very difficult for our bodies to stop an infectious disease.
Do you know what it takes to be a super dodger?
Scientists have only been able to identify two instances of true virus superdogers. People are resistant to a virus because of a specific genetic change. It slides off their cells like water sliding off a glass window.
In 2003 a team in London showed how some people don't get a stomach bug. The researchers were able to find a way to stop the virus from making a molecule.
In 1995 researchers in France figured out why some people didn't get sick from the disease. Over the past 10 years, further studies have shown that these super dodgers actually get sick from the parasites and don't show symptoms.
People who are protected against HIV are the most famous super dodgers. They were studied in the early 1990s by Landau and his colleagues.
His team was close to solving the puzzle. They found a big clue one morning. They had set up an experiment the night before to find out which molecule HIV needed to cause harm. Spectacular results came from the experiment.
Scientists had thought that HIV entered cells in a different way. It needed some assistance. HIV requires a molecule on the surface of the cell to open the door. The virus only sticks to the cell's surface if there is no CCR5. The virus is knocking at the door, but no one is opening it. He said the door was locked.
"That was a eureka moment," he says. We found something that had never been seen before.
The findings were quickly written up by the group of people. He ran to the FedEx store to submit the paper, knowing that other teams were going to have the same finding soon.
He says that in those days you couldn't just submit your paper online. You had to send a hard copy of it. I was supposed to go to the FedEx store to get the paper sent on time.
The final piece of the HIV puzzle was solved by Landau and his colleagues after only a few weeks. We were surprised that it all happened so quickly.
Two people completely resistant to HIV were mapped out by Landau and his colleagues down the hall. It was lo and behold. The two people had the same genetic abnormality. The group reported in the journal Cell that it cripples the molecule so that it doesn't show up on the cell's surface. Without CCR5 HIV can't get into the cell.
He says that if you put a lot of virus particles on those cells, they won't get sick. The story of resistance to HIV was clear.
The field of HIV was completely changed by the discovery. It led to the first and only way to cure a person of HIV with the use of gene editing. It showed scientists that a single change in a person's genes could make them impervious to infections. They could be a true super dodger.
Many labs looked to see if the same thing could be done with this virus. They were inspired by the story of CCR5 and went looking for changes in the genes that are needed for the disease.
Is there really a group of people who are super dodgers?
The situation for people who don't know they're HIV resistant is more complex than for people who know they're HIV resistant.
CCR5 is used to open the cell's door, instead of the other way around. The people can't live without it. Thereceptor regulates your blood pressure. It's not possible to simply knock out the ACE2 receptor. You're not going to have a lot of people walking around with no ACE2
There could be more subtle alterations in ACE2 which could play a role in resistance to the disease. There doesn't seem to be an obvious and dramatic change.
It's possible that people have genes that don't protect them from getting infections but do protect them from getting sick, and that's what he's suggesting.
If you have one of these, you'll be a mini dodger. It is possible to deny the virus entry into the cell. Your immune system is likely involved.
The team at UC San Francisco has found that.
People who test positive for COVID but don't show any symptoms have been studied. She doesn't even have a sniffle or a sore throat. They are completely normal.
After analyzing more than 1,400 people's genes, they found a way to help a person clear out a disease so quickly that they don't have to worry about symptoms.
During the earliest stages of an infectious disease, the HLA gene is important. According to Hollenbach and her colleagues, having a particular variation in that gene increases a person's chance of not being noticed. They reported those findings online.
They've shown how this works. It has to do with your immune system getting ready for the outbreak.
When a virus enters a cell, the immune system needs help. That signal causes your body to make weapons that are designed to fight the disease. Antibodies and T cells are included in these weapons. Your immune system will be able to clear up the infection quicker once these weapons are available. These weapons are difficult to make. The delay allows the infections to spread.
Is it possible that your immune system already had weapons that were specifically designed to deal with the deadly disease?
Hollenbach and her colleagues showed that some people have T cells that are pre-programmed to recognize and fight off the disease. There is no delay in the creation of weaponryfic. The place is already there.
"Your immune response and these T cells fire up much more quickly than in a person who doesn't have the same genetic abnormality," Hollenbach says. For lack of a better term, you nuke the infection before you even start to have symptoms.
This is the kicker. If you want to have these pre-armed T cells, you need to have been exposed to a coronaviruses.
She says that most of us have been exposed to cold coronaviruses. We all make T cells to fight off colds. Just by chance, these T cells you make can also fight off the disease if you have the same genetic abnormality.
She says it's definitely lucky. This is a common variation. It's possible that 1 in 10 people have it. It goes up to 1 in 5 in people who aresymptomatic.
While Hollenbach and her team continue to look for more mini dodger genes, Casanova and his colleagues are trying to determine if there are true super dodger genes. He is looking for people to take part in his study.
He says that you fill out a questionnaires online about your exposure to the disease. A testing kit is sent to you if you meet the criteria of a super dodger. You spit in a cup and send it back to Casanova.
He says that they will sequence your genome. In a group of 2,000 to 4,000 people, we hope that some people will have genes that tell us why they're resistant to infections.
One day, like with HIV, that finding will change the field of COVID research and lead to a vaccine that will turn everyone into a COVID super dodger.
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