Cooking up a medical revolution

Dr. Dorit Arad has come up with a way of detecting pathogens instantly - an innovation that could change the way medicine is practised.

bacteria 88 (photo credit: )
bacteria 88
(photo credit: )
They're out there, and they're after us - viruses, bacteria and other pathogens that ignore personal and national boundaries. They spread not only by direct contact but also by plane or migrating birds. Infections with these pathogens are usually diagnosed too late - when victims already have symptoms, can't be treated effectively and have even infected others. In recent years, the phenomenon has threatened many parts of the world with a series of diseases ranging from SARS (severe acute respiratory syndrome, which killed almost 800 people six years ago and then dissipated) and Legionnaire's disease to influenza and West Nile virus (which killed 29 Israelis and infected 400 more in 2000). There is no known cure for either. But a brilliant Israeli organic chemist who has set up a series of startup companies in Israel and the US to develop her patented technologies seems to have a solution. If Dr. Dorit Arad, who has dozens of patents or patents pending, is right, she could become very wealthy: The annual world market for quick diagnostic kits for such pathogens is estimated at around $40 billion. She told The Jerusalem Post in a recent interview that the technology developed at her Ness Ziona company, Modules for Novel (MND) Diagnostics, has even wider applications in customized treatment for cancer patients. She was working in the US developing antiviral drugs for a company named eXegenics when the SARS epidemic hit and got her so nervous about catching the contagious virus that killed almost 10% of its victims that she was "hysterical and even wore a face mask." THE THREAT also caused panic among health authorities here, who sent doctors to the airport to examine any passengers with pneumonia-like symptoms, put them through tests that took days and sent suspected SARS victims into quarantine for weeks or more. She decided to focus on the development of detection kits, not using the standard technique of finding antibodies, but focusing on enzymes present when live viruses multiply. Using a small saliva or blood sample mixed with patented materials, the liquid in a test tube changes colors - like a pregnancy test kit - in a few minutes or becomes fluorescent when a specific virus is present. No specially trained personnel are necessary, said Arad. This makes mass screening possible in schools, airports, clinics, hospitals or other locations. Born in Haifa to parents born in Poland - her father an Egged bus driver and her mother a kindergarten teacher - Arad had no role models for going into science. "I wasn't very good in most subjects in high school, but I knew all the answers in chemistry. I had an excellent woman teacher in that subject." She didn't mind the chore of washing test tubes, and today is also an excellent cook. "Chemistry involves mixing elements together, as if you are in the kitchen. I know many chemists who are also excellent cooks." AFTER SERVING as a trainer of medics in the Israel Defense Forces, Arad decide to forgo the study of medicine and went to Haifa's Technion-Israel Institute of Technology to study organic chemistry, earning bachelor's, master's and doctoral degrees there. Prof. Yitzhak Apeloig, a leading chemist who is now Technion president, was then supervisor of her research. "I chose organic chemistry among all the fields because it was the best subject for understanding life mechanisms. I wanted to do practical things more likely to help people." By now, she has authored over 50 publications and received numerous awards, organized international meetings, created extensive global collaborations with world-class scientists (including 1998 Nobel laureate Dr. John Pople), and served as professional adviser for several pharmaceutical companies. Fortunately, Apeloig pushed her to learn basic science, which more than ever leads to practical applications. "No one would have thought decades ago that nuclear magnetic resonance would lead to magnetic resonance imaging (MRI), the main tool for scanning patients," she says. Basic scientific principles helped in her quest for rational drug design. Arad did her post-doctoral fellowship at the University of California at San Francisco and returned to become a biotechnology lecturer for nine years at Tel Aviv University. In her research in Israel, she "looked at structures of proteins and suit structures to inhibit them or speed them up," she recalled. "I developed a new technique based on chemistry and the mechanism of reaction." THEN SHE moved to the US, starting with viruses and drug design at eXegenics in Dallas, Texas. The company bought her technology. After doing successful research for five years there, she bought back the rights from the company and returned to Israel, establishing MND Diagnostics four years ago and doing collaborative work with a company in France. Her first diagnostic kits for viral diseases, whose next hurdle will be US Food and Drug Administration approval, could go on the market next year. Clinical studies show they are very reliable and accurate. "My target was an enzyme called 3C. The 3C enzyme has an important role in the maturation of viruses ranging from hepatitis A and enterovirus to polio and foot-and-mouth disease. We had inhibitors with a potential for drugs, used a substrate and found parts of virus with the enzyme. The technique," she noted, works on many viruses, but one has to develop the suitable substrate for each. MND Diagnostics, she said, was established to provide timely responses against emerging diseases by utilizing novel routes of diagnosis and treatment. MND Diagnostics is currently developing a quick test for cytomegalovirus (CMV), which is very risky for fetuses and people with weak immune systems, including cancer and HIV/AIDS patients. Most healthy people infected with CMV are symptomless. After infection, the virus remains latent for the rest of the individual's life, though it can be found in bodily fluids. Fetuses infected by their mothers before birth are at high risk for complications such as low birth weight, smaller-than-normal brains, seizures and liver problems. Most babies with CMV disease will survive, but with a high risk of complications including mental retardation, hearing loss or vision impairment. These problems usually affect the fetuses of women who were newly infected during pregnancy and not those carrying the signs of an old infection, but it has been difficult to differentiate between the two. Thus a test to detect fresh CMV infections, when the virus is reproducing, would be crucial - and that is what Arad has done. "We have a fast CMV kit that is not yet on market because it needs FDA approval. We have a number of clinical results already, and it will also be useful for testing potential transplant recipients. Today's tests take much longer." Also being targeted are SARS, the rhinovirus that causes the common cold, coronavirus, rotavirus, hepatitis C and even HIV-1. But MND Diagnostic's first product on the market will be a speedy kit to detect viral meningitis, and later, there will be one for bacterial meningitis. The need for this, said Arad, was pointed out by Prof. David Greenberg of the pediatric infectious disease unit at Beersheba's Soroka University Medical Center, who is now medical director of MND Diagnostics, which currently has 15 employees. The company, of which she is chief technology officer, will be able to manufacture kits for the world from its rented Nes Ziona facility. "Today," said Arad, "it takes days to detect bacterial meningitis. Children have to go to hospital for tests and then are sent home until the results are ready. In the meantime, many are given strong antibiotics, causing resistance. With our test, it will take three minutes. Clinical trials were held this year. We will be prepared to market the tests after FDA approval in the second half or third quarter of 2009." A kit for quick detection of bird flu in birds will be among the first products. Arad's technology can be applied as kits not only to detect well-known pathogens but also newly emerging viruses. Her enzyme-based method can also be applied to mutated viruses whose family can be identified. There is also a potential for specific kits to detect any bacterial diseases or fungal infections that have enzyme activity. "Enzymes are also important in cancer markets. We are working on kits to detect enzyme markers for cancer. If a biopsy for prostate cancer is positive, for example, the patient has to undergo more tests like a biopsy. We believe we can develop a more accurate PSA test that will avoid unnecessary biopsies," Arad suggested. "Another one of our ideas is to detect the cascade of coagulation profile in blood that would provide early detection of stroke." ARAD NEVER dreamed that applications of her theories would go so far. "We have been so busy. Now is the time to start writing articles for publication. We have lots of advisers from Israeli hospitals." In a decade, she predicted, "our kits will change the practice of medicine. Doctors in their clinics will test patients for diseases in minutes. There will also be home tests." Eventually, Arad concluded, the kits could lead to prevention of disease, such as cutting down infection in hospitals caused by methycillin-resistant Staphylococcus aureus (MRSA) bacteria, which are resistant to a large group of antibiotics. "I started working on the technology with the idea of simple detection kits to stop outbreaks in airports," Arad stressed. "I never imagined it would turn into a broad breakthrough technology arousing world-wide interest. Indeed, only in the past few months we have begun to present it at international forums in the US, Italy, Japan and Britain, and at every convention it was highly praised and raised a lot of interest. As a result, new contacts with large pharmaceutical companies have been launched." There are thousands of potentially dangerous virus strains and bacteria that cause all kinds of mischief, but they can be assured that Dr. Dorit Arad is on their tail.