The SMARTube enables antibody production, in a small blood sample, within days from infection, without having to wait for the body to produce antibodies weeks or months later. Testing for HIV and Hepatitis C (HCV) has come a long way over the years – but there is still a mortally dangerous shortcoming in the technology that detects whether a person is infected.
That’s why the Israeli technology SMARTube, developed by Smart Biotech’s Dr. Tamar Jehuda-Cohen – has such far reaching, life-saving implications.
According to the National HIV Prevention Conference, over a million Americans are living with HIV/AIDS, with 24-27% of that number undiagnosed and unaware of their HIV infection. In 2004, the estimated number of diagnoses of AIDS in the US was 42,514.
In addition, over 4,000,000 Americans are infected with HCV. About 85% of individuals acutely infected with HCV become chronically infected. Hence, HCV is a major cause of chronic (lasting longer than six months) hepatitis. Once chronically infected, the virus is almost never cleared without treatment. In rare cases, HCV infection causes clinically acute disease and even liver failure.
The way to identify HIV and HCV carriers is by detecting the antibodies against the virus in the patient’s blood. However antibodies against HIV and HCV take weeks – or months – after infection to develop in the body. This in essence creates a ‘window period’ in which infected people will be considered non-infected as long as they do not produce antibodies in their body.
According to Jehuda-Cohen, Smart Biotech’s Chief Technical Officer, the implications of this time gap are deadly – infected people are told they are not currently infected, and they should come back and be tested again in six months. These individuals pose a greater risk to their community than those that were not tested at all, because:
A. They have a ‘certified OK’ not to use any precautions against infecting others.
B. They have a ‘certified immunity’ against getting infected, as they engaged in high-risk behavior and did not get infected.
“Almost every person that is misdiagnosed because he or she are in the window period are people that have been leading a high risk life, and what you’re telling them – because until the SMARTube, a better tool didn’t exist – is ‘you’re not infected!’, she told ISRAEL21c.
“The natural response is then… ‘hey, I know what I’ve been doing – and I can continue doing it – because I didn’t get infected.'”
According to Jehuda-Cohen, it has been calculated that infected people in this situation will infect 50 people a year on average.
In addition, blood donated at blood banks during the ‘window period’ – and therefore test negative by current testing – can be transfused into patients, and may infect them. The extent of the problem increases with the rate of spread of the epidemic.
“The only way to curtail the epidemic is to have earlier detection of the virus,” says Jehuda-Cohen.
She has done just that. The SMARTube enables antibody production, in a small blood sample, within days from infection, without having to wait for the body to produce antibodies weeks or months later.
The technology is the culmination of more than 12 years of work by Jehuda-Cohen, an immunologist with a PhD in immunology from the Technion – Israel Institute of Technology. She did her post-doctoral work at Emory University in Atlanta (“just down the street from the Center for Disease Control”, she notes), where she began on working in AIDS research.
Jehuda-Cohen doesn’t fit the usual image of a scientist who has made a discovery of world importance. The religiously observant Israeli mother of seven possesses a refined, sophisticated demeanor. And unlike many scientists, she’s able to explain complicated processes in everyday terms.
“What happens when a person is infected with HIV is that the immune cells in the body see the HIV and want to scream and say ‘we’ve seen it – we know how to make antibodies against it!’ But the HIV puts a masking tape on their mouth so they can’t scream so nobody knows what they saw. So what we do in the SMARTube is unmask the mouths of the antibody producing cells and give them a microphone,” she told ISRAEL21c over lunch in a Jerusalem hotel.
She then patiently provides a general background on immune diseases for the medical novice.
“With most infections, the immune system sees the foreign structure and begins making antibodies within a few days – usually you can detect them within 5-7 days of infections. Antibodies are a good marker to use for detecting any infections because they’re available in a drop of blood, and you don’t have to go into the liver or the lungs to fund a liver or lung infection.”
However, with HIV and HCV, the most devastating and chronic infections, the antibodies don’t show up after five or seven days. It could take weeks or up to many months to see any antibodies in the blood of HIV or HCV-infected patients.
“As long as there are no antibodies, these patients are diagnoses as non-infected. This is called the window period – the time between infection and the detection of antibodies, and that’s where my research comes in,” she said.
It’s a phenomenon that came to prominence in the mid ’90s when people who had been tested and were diagnosed as ‘sero-negative’ went out and infected others.
“Obviously you can’t infect somebody if you’re not infected. And that’s when the realization came that a test was being used that does not diagnose everybody,” she said.
Since then, the medical community has been trying to solve the ‘window period’ problem with modest success. Diagnostic companies and kits have made strides to detect lower and lower levels of antibodies that enable diagnosis several days earlier.
Other methods of looking for proteins or antigens in the virus have likewise been able to shorten the window period by only a few days. This test – called p24 antigen test – is of minimal value. “It has proved to be very non-cost effective and inefficient,” she said.
The greatest stride has been in the testing of the viral genome – the nucleic acid of the virus, which has shortened the window by an additional 12 days or so, she said. But this very expensive test is only positive when there is enough virus in the blood, and this too can take weeks or even months before it happens. Here again, an infected person might test negative
“The fact is that there are no antibodies in the blood because the production of antibodies is suppressed. So there’s a period where no matter how sensitive you make your kit, you will not detect antibodies – because they’re not there,” said Jehuda-Cohen.
“The core of the technology is overcoming the specific immune suppressants of the body. A few drops of blood are placed into the SMARTube and a solution inside helps the cells of the immune system overcome the suppression, and pushes them into an extremely fast process of antibody production.”
The end result? “We can detect those individuals already infected when nobody else can – because they’re still at the very early stages of the window – where there’s no other technology today that can detect them.”
According to clinical studies on high risk populations conducted in Israel and other countries, the SMARTube successfully enables the detection of all the patients who are diagnosed in the conventional testing – but also detects the virus in additional patients that are infected, but otherwise would have gone undetected at that testing time.
“How much earlier can we detect them? We don’t know the point of infections, so nobody can know how long it takes. But in our studies, we’ve seen that it can take weeks or months before the antibodies on their own will reach detectable levels.”
Sensitive to claims that a test also needs to be conducted in the real world – outside of a shiny lab in a scientific paradise like Israel, Smart Biotech has also conducted trials in other countries, under less than optimal conditions.
“It’s very important – not for the sake of proving that it works, because we’re beyond that – but to show to ourselves first and then to potential end users that this is something that can be used anywhere in the world. It’s very nice to do it in nice modern Israel, but can you take this device and give it to somebody in Africa to use with instructions on how to use it? The answer is yes.”
Jehuda-Cohen’s partner in the vision of the SMARTube is Smart Biotech’s founder and CEO Yisrael Serok, a retired government official who has been interested in this technology since learning about it five years ago.
“At some point we were talking and we said, ‘you know what, let’s start the company. We’re very close to having a product ready so… let’s go, it’s time,” he told ISRAEL21c. “So two years ago, we officially started the company, and now we’re starting to sell the SMARTube.”
Having received the CE Mark (the regulatory requirement in Europe for its registration and marketing) as a blood collection and pre-treatment device, the SMARTube is available for use in hospitals, diagnostic labs, blood banks for health or life insurance uses, “basically anywhere blood samples are taken for HIV ttesting,” said Jehuda-Cohen.
US approval by the FDA is in the plans for later this year, accordin to Serok.
While the top-secret SMART-solution in the SMARTube is produced at the company’s Rehovot facility, the actual device can be manufactured by partners in whichever the country is being targeted.
“Filling it into tubes or vacuum tubes is the process that can be done by outsourcing, where our partners in China can do it in China, where our partners in Europe can do it for the rest of the world. We are not planning on having large-scale production. We want to stay small, smart,” said Serok.
For Jehuda-Cohen and Serok, the SMARTube has been an obsession with an altruistic goal, of detecting the HIV virus as early as possible. But even they realize that it’s far from a cure for AIDS.
“The rule of thumb is the earlier you detect the better you can treat. Treatment and cure are not the same thing. You cannot cure an HIV infection. We can hold it in place,” said Jehuda-Cohen.
“There are parts of the world where you diagnose, but treatment is not an option. So why diagnose? The answer is that we are trying to detect people all over the world as early as possible because it helps us focus education intervention for changing habits. The most important key for curtailing the epidemic is well targeted education, Early detection is the key.”