“We were widely acknowledged as the experts in failure. No one we know had failed as much as we had,” says Prof Karim.
Internationally acclaimed South African scientist Professor Salim S Abdool Karim, lauded for his research on HIV/Aids and COVID-19, has some sound advice for young scientists hoping to make major scientific discoveries: a long road lies ahead. Keep at it. Collaborate. Seek out partnerships. Remember your humanity. And don’t make any predictions.
He offered these key lessons during the inaugural public lecture of the African Research Universities Alliance (ARUA), held at Future Africa on 14 September 2023.
The lecture, “Aids and COVID-19: A tale of two pandemics”, saw Prof Karim condensing his research journey of 33 years and 500 journal articles into about an hour.
‘The experts in failure’
Since setting out on the journey in 1990 to understand the Aids pandemic and find ways to deal with it, Prof Karim has experienced many ups and downs.
One of the lowest points was repeated failures in developing vaginal foam or gel products to protect teenage girls and young women – who have the highest rates of HIV infection in Southern Africa – from becoming infected with HIV.
“We had tested over eight different products and every one of them had failed,” Prof Karim said, referring to the disappointing trial results he and his wife, Professor Quarraisha Abdool Karim, had encountered over a period of about 18 years.
“We were widely acknowledged as the experts in failure. No one we know had failed as much as we had,” he said.
“How on earth do you stay and carry on? We had to. The problem was too big; the challenge too great. We had to persevere and so we did. We made Tenofovir gel,” said Prof Karim.
Tenofovir gel, which has a powerful safety profile and is highly effective in suppressing the HIV virus, was ready to be trialled as a pre-exposure prophylactic (PrEP) in 2006. Despite an article in a top international journal warning that it was doomed to fail, the trial went ahead, delivering findings that were lauded across the world when they were announced in 2010.
The next challenge: the microbiome
Meanwhile, another challenge had arisen. The Karims had discovered that Tenofovir gel was less effective in protecting women from HIV infection when they had genital inflammation.
This led to research on the vaginal microbiome and the discovery that women have better protection against the virus when certain bacteria, lactobacilli, are present, and are more vulnerable to infection when these bacteria are depleted.
“The microbiome is defeating us. We have to sort this problem out,” said Prof Karim. While the solution for this has not yet been found, he is working on a new programme with the Gates Foundation to develop a capsule to release the right bacteria into the vagina.
“Cross fingers that we get a positive answer to reduce the risk of HIV infection,” he said.
Yet another piece of the HIV/Aids puzzle that still needs to be solved is the challenge of non-adherence to medication such as PrEP, that women have to use or take daily to protect themselves against exposure – for a disease they do not have.
“Adherence is the big challenge,” Prof Karim said, adding that a possible solution is the use of a broadly neutralising antibody that is highly potent against the virus. Known as CAP256, after the woman in whose blood it was found, the antibody could potentially provide protection against HIV infection for between six and nine months.
The Karims and their research partners are currently busy making a six-month injectable containing an antibody combination, while undertaking a study on whether or not this could be effective in actually preventing HIV infection.
The results are expected in 2024.
If CAP256 is shown to be effective in preventing infection, it could then potentially be back-engineered to set up a sequence of HIV vaccines. This will not happen overnight, though.
“A long road yet lies ahead, and that road I am telling you will not be undertaken by any of us. It is the next generation who will do that.”
In it for the long haul
Addressing up-and-coming scientists hoping to make major discoveries, Prof Karim said: “I know you can get disheartened. I know that you will you see failure and you will want to choose something else.”
His own experience, however, showed that no significant innovation comes without persistence and perseverance. “It’s a long, long road, because we are making completely new medicines and you have to be ready to take on this journey.”
Turning to the COVID-19 pandemic, Prof Karim said a key lesson for the future was the importance of interdependence, shared responsibility and global solidarity in dealing with a pandemic. “And we have to find our humanity and care as much for others as for ourselves. If we don’t, we are not going to do much better in the next pandemic.”
He recalled a personal lesson learnt in August 2021, when a journalist from Bloomberg insisted he answer her question on if and when the next COVID-19 wave could be expected. “She asked me and asked me. She wore me down and I said something that I would not normally have said. I said that based on a very simple analysis, we can expect the next wave on 2 December and that the wave would be expected to last for about 75 days. “
Although his prediction turned out to be exact, Prof Karim regretted making it as it sparked off a global social media buzz and he even found himself being fact-checked.
“Don’t make predictions,” he advised young scientists. “It’s not a good idea. Even if they come right, they have huge consequences.”