Breakthrough Dividend
Executive Summary

Given the world's major needs—food, health, energy—biotechnology is one of the most exciting and potentially profitable fields imaginable. The United States, with its advanced management and marketing expertise, and Israel, with its highly innovative R&D community and high-quality/moderate-cost workforce, are particularly well-placed to benefit from strategic partnerships.

Biotechnology is already big business. American has more than 1,000 biotech companies, with $3.5 billion in 1992 sales (more than 90 percent in human health products), which directly provide almost 100,000 American jobs. Thousands of products are in the pipeline, under development or awaiting regulatory approval. These should emerge in the next few years, signaling the field's next, more mature phase.

Israel, given its much smaller size, domestic market and access to venture capital, has only about 50 domestic biotech companies, employing 3,000 Israelis. Israel's intensive interest and investment in science, however, give her a scientific status and high-tech impact typical of industrialized countries many times her absolute size. The specific Israeli innovations in biotechnology, moreover, create opportunities for strategic alliances that can benefit the companies involved and, more broadly, the citizens of Israel and the United States.

The United States and Israel have long been partners in a variety of mutually beneficial endeavors, many funded by binational foundations (BSF, BARD, BIRD). New structures, such as the U.S.-Israel Science and Technology Commission (USISTC), recently established by President Clinton, seek to further extend the competitive edge of both the American and Israeli high-tech sectors through increased cooperation. The USISTC's Working Group on Biotechnology, Israel's National Committee for Biotechnology and a new U.S.-Israel Biotechnology Council have all been particularly active.

Even before the new governmental emphasis on cooperation in biotechnology, many U.S. companies established Israeli subsidiaries to benefit from generous Israeli government R&D incentives, Israel's highly-trained, highly-dedicated, moderately-priced workforce and free trade agreements with both the U.S. and Europe. The Binational Industrial Research & Development Foundation (BIRD) has also supported joint projects between American and Israeli biotech firms.

The abundance of Israeli biotech innovations warrants American attention. These include mice with transplanted human bone marrow that can produce human antibodies; a juvenile-onset diabetes treatment that is 90 percent effective in mice; drugs that decrease recurrent attacks of multiple sclerosis, boost human interferon production and modulate blood clotting and safe new vectors useful in human gene therapy. Israeli researchers also developed new processes for the commercial production of important recombinant proteins such as human and bovine growth hormones, human superoxide dismutase (SOD), human tissue plasminogen-activator, human beta-interferon and human interleukin-6, a promising activator-component in experimental anti-cancer vaccines.

Diagnostics, particularly monoclonal antibody-based test kits, were among Israel's first biotech successes. The FDA's stringent Good Clinical Practice (GCP) regulations for pharmaceutical testing force most Israeli researchers to license their new drug discoveries before major (Phase III) clinical trials. In contrast, Israel moves its diagnostic discoveries from the laboratory to the marketplace in record time (3-5.3 years) at record low budgets ($0.9-1.2 million), compared to their U.S. counterparts (8-11 years, $25-30 million). Starting with the world's first ELISA test for chlamydia in 1989, Israelis soon developed high-quality tests for Epstein-Barr virus, cytomegalovirus, herpes I and II viruses, mycoplasmal pneumonia, TSH, hepatitis A and B, anti-sperm antibodies and early pregnancy. They now have simple, ultra-fast and highly accurate two-minute tests for urinary-tract infections and AIDS. Israel's academic researchers are now shifting their attention to DNA and RNA-based (rather than antibody-based) tests for cancer and other diseases. New products for monitoring blood sugar and diagnosing Alzheimer's disease are also under development.

Although foreign experts consistently praise Israeli agricultural biotechnology as unique, agricultural R&D support and commercial activity tend to lag behind that for medical applications. Israel is blessed with rich genetic resources. The home and center-of-diversity of such grains as wheat, oats and barley, Israel has been working with the U.S. Department of Agriculture on new varieties since 1909. It also has the advanced biotechnology to exploit valuable genes. Recent successes include increasing yields through the production of chromosome-engineered pasta and bread wheats and raising genetically-engineered tobacco plants that can protect themselves from viral attack. Several other virus-resistant transgenic plants have already been patented. Israeli ELISA-based plant diagnostic tests already protect most U.S. seed potatoes from potato leaf-roll virus. Other researchers have developed plant virus diagnostic kits for many other viruses, including those affecting beans, tomatoes and tobacco.

Another Israeli specialty is biological control. Trichoderma fungi, often improved by protoplast fusion, prevent damping-off disease and Fusarium wilt, while boosting plant growth. Special non-virulent Rhizoctonia strains have similar effects. Other researchers have discovered a highly potent antiviral agent, IVR, in tobacco. They have already identified the IVR gene, inserted it into bacteria and can now produce IVR by fermentation. Transgenic IVR-producing virus-resistant crop plants are next. Israel's well-known Bacillus thuringiensis var. israelensis(BTI) produces a potent, highly selective, environmentally-safe toxin that kills mosquito and black-fly larvae. BTI formed the basis of a recent successful mosquito control effort in Massachusetts and a new U.S.-Israel-Jordan biocontrol initiative sponsored by the U.S. Agency for International Development.

Animals are a major agricultural money-maker; the U.S. produces $72 billion of cattle/dairy/poultry products annually. New Israeli biotech innovations help breed leaner chickens and more fertile cows, diagnose Rift Valley Fever (RVF) and anaplasmosis in cattle and screen for Marek's disease in poultry. Israeli investigators and U.S. collaborators have developed new vaccines against RVF, Newcastle disease and Mycoplasma gallisepticum. They have even produced and successfully tested a vaccine against fish meningitis for use in aquaculture. Perhaps the most innovative new Israeli vaccine reduces tick-borne diseases in cattle by binding special receptors located near the tick's mouth, which maintain the feeding response. They are now using a similar strategy against lice.

The report concludes with recommendations on how potential partners, and Israel itself, could best benefit from Israeli biotech opportunities. These include the need for a Biotechnology Innovation Development Fund to strengthen the weakest link in Israel's laboratory-to-market chain, Precompetitive Industrial Research Centers, Israeli Contract Research Organization's and Clinical Research Associate training programs capable of meeting the FDA's GCP requirements for clinical trials and further strengthening of academic-industrial linkages. In particular, Israel's high recruitment rates and low dropout rates could significantly speed up U.S. clinical trials, and increase U.S. pharmaceutical competitiveness, once FDA GCP's are met, to the mutual benefit of both countries.