Israeli bioterror experts coming up with the right answers

‘Using biosensors [to detect] chemical warfare is an area we have developed over the last year’ – Itamar Willner, a professor of organic chemistry at the Hebrew University of Jerusalem.Bioterrorism has been in the minds of millions of Americans ever …

‘Using biosensors [to detect] chemical warfare is an area we have developed over the last year’ – Itamar Willner, a professor of organic chemistry at the Hebrew University of Jerusalem.Bioterrorism has been in the minds of millions of Americans ever since the ‘anthrax letters’ were sent just after 9/11.

Unlike conventional terrorism, where a bomb blast is a clear sign that something has happened, biowarfare methods such as spraying viruses into the air or polluting water sources are silent and often leave no visible trace. How do we know if something has happened, and, more importantly, what do we do about it? Israeli scientists are coming up with answers from several different angles.

“We have no real time systems for detecting biological agents in air,” said Dr. David Franz, former director of the US Army’s Medical Research Institute of Infectious Diseases, in his keynote speech at an International Workshop on Defense to Biological Threats held at Ben-Gurion University in early December. What is needed, he told the workshop, are diagnostics and sensors to detect if a bioterror event has occurred, vaccines to protect the population, and forensic attribution, so that the perpetrators can be tracked down.

Detection is the first challenge, and Israel’s university labs are coming up with many answers. Itamar Willner, a professor of organic chemistry at the Hebrew University of Jerusalem, told the workshop about his work on combining bioelectronics and nanobiotechnology; in other words, bringing together biological materials with tiny electronics.

“Using biosensors [to detect] chemical warfare is an area we have developed over the last year,” he said. It is known that chemical warfare agents like Ricin, used in the Tokyo subway attack, Sarin and Mustard Gas inhibit a certain enzyme in the brain which blocks neurological function. Willner’s concept works backwards: if you can detect that this enzyme has been blocked, then you will know that chemical agents have been released. Willner and his team are developing a tool to do this using a gold nanoparticle, a billionth of a meter in size, which changes color depending on the amount of enzyme present.

Avi Shanzer, a professor of organic chemistry from the Weizmann Institute of Science in Rehovot, is working on a diagnostic kit for detecting biological agents.

“They have to be real-time, fast, and not sensitive to temperature, and easy to use without training, as well as cheap,” he said. His system is based on iron. “There is no life without iron,” he told the workshop.

His detection methods relies on the iron-carriers in the body called siderophones. However, it is not just humans who need iron; bacteria also need it and they also use siderophones to provide them with iron. Shanzer is developing synthetic siderophones which will light up when a certain bacteria such as e.coli or anthrax is present and trying to get iron.

Ben-Gurion University’s Angel Porgador, a senior lecturer in microbiology and immunology, has yet another take on detection: “The immune system has a repertoire of molecules to detect pathogens,” he said. “Instead of trying to generate new molecules [to detect biological agents] can we identify these molecules from the immune system and use them to identify pathogens [used in bioterrorism]?”

Porgador is studying how the body’s natural ‘killer cells’ identify a foreign invader that has entered the body and is infecting the cells, latch onto the invader and destroy it. He is also working the other way, and studying how the invading molecules recognized the body’s killer cells, to see if this can help. He already has killer cells that recognize pox viruses like smallpox and West Nile Virus, and is working together with Robert Marks of BGU’s biotechnology engineering department, to put these molecules on a biosensor to detect biological warfare.

Marks is developing biosensors which use fiber-optics for many different applications. “They are dual-use,” he said. Not just for bioterror, these sensors, “can be used for medical diagnostics.”

There are biosensors on the market, but at a cost of $100,000, they are not a cheap solution. Marks is developing the BioPen, “a handheld, near real-time collector of a sample, from blood, urine or water.”

The BioPen will be a one-use-only, disposable probe. A biological entity, which could be cells or antibodies or enzymes, will sit, in gel, on the tip of the probe to detect the virus or bacteria. When it detects something, it glows, and this light is then transmitted along optical fibers to a photodetector which measures the light emitted. The test takes around 90 minutes. Marks is developing probes to test not just for viruses, but also for water contaminated with poisonous substances such as mercury.

Perhaps the development which is closest to moving from the laboratory to the real world is the cellular equivalent of the miners’ canary. Shimshon Belkin, professor of applied microbiology at the Hebrew University, doesn’t need a whole animal: he is developing a biochip with live cells on it to detect toxic substances.

“Our system is about the detection of chemicals,” he said. “The threat is the intentional poisoning of a drinking water source. The scenario is not that far fetched and we need a broad-spectrum early warning device, but no such device exists.”

Belkin’s theory is that while chemical and biological molecules can be used to detect a specific virus or contaminant, like a human being who will start feeling ill if poisoned “only a live cell can [answer the general question of whether] a sample is toxic. I am designing a system that will report if the cell is feeling unwell or not.”

He has genetically modified bacterial cells to light up when their DNA is being attacked, and he places these cells on a disposable, credit-card-sized biochip. The biochip is dipped in the sample and then inserted in an instrument which will analyze the cells’ reaction to the water. The aim is not to detect a specific toxin, but just to rapidly answer the question: Is this water safe to drink?

Belkin has a prototype, but says there are still questions to be answered and more work to do. “Now, the system responds in 20 to 30 minutes; we want to get that down to under 10 minutes.”

These projects are just some of the work going on in Israeli universities across the country to try and make the world a safer place. This workshop brought together scientists involved in this work from across the country, and abroad, including the US and Uganda, to try and create a forum for cooperation and ideas.

“I have been thinking about this since before 9/11,” said Leslie Lobel, from BGU’s Virology department, who is studying the Ebola virus and who organized the workshop together with Robert Marks. “[Bioterror] just happens to be a hot topic right now. I don’t think there is enough emphasis on the academic involvement in this field.”

Venture capital companies are investing in technology start-ups which don’t necessarily have a solid scientific basis to their innovations, Lobel says. “We are taking basic science and bringing it together to make something feasible.” He is hoping that BGU will establish a center for biodefense. “You can’t leave it too late,” he said.