The time when a scientist could sit with his assistants in a lab and develop a new medication has passed. Today, drug developers need a whole multidisciplinary team, each contributing specific expertise. As a result, hospitals, pharmaceutical companies and medical schools have been changing the way they work.
The School of Pharmacy of the Hebrew University Medical Faculty in Jerusalem has now taken such a step by establishing the Institute for Drug Research (IDR) - the first in the country - as a way of getting top minds together to create a facility that will attract financial support from donors and industry. Israel's Teva pharmaceutical company has committed itself to invest a lot. In teams and as individuals, the institute's researchers have already discovered new drugs and invented novel drug-delivery platforms for a variety of clinical disorders including allergies, cancer, age-related and neurological diseases, brain trauma, diabetes and drug addiction. Over the years, 13 start-up companies have been established based on research by the institute's current research staff. Collectively, they have registered over 200 patents, totaling more than a quarter of HU's approved patent applications.
FOUR NOVEL drugs developed by the institute and commercialized by Yissum (the university research and development company) are currently on the market. The best known is Exelon, which delays the onset of Alzheimer symptoms. Several other drugs are currently in various stages of development.
A conference to mark the IDR's founding was held earlier this month at the capital's Inbal Hotel and attended by over 100 pharmacologists and students. Prof. Israel Ringel, head of the pharmacy school and new head of the Institute for Drug Research (IDR), said he reorganized the school to accommodate the institute's interdisciplinary approach, which will target medical problems and work to solve them by developing specific drugs and other treatments. "It was established to meet the complexity and versatility facing drug research and development today," he said. "We believe that training the new generation of leading scientists in drug research is a national mission."
The prominent guest speaker at the conference was Prof. Leslie Benet, widely described as "the world's best and best-known biopharmaceutical scientist." A Jew born in Cincinatti, Benet is a professor and former chairman of the department of bioengineering and therapeutic sciences at the University of California, San Francisco (UCSF), former president of the Academy of Pharmaceutical Sciences and the American Association of Colleges of Pharmacy and founder of the American Association of Pharmaceutical Sciences. The UCSF is the same university that produced Prof. Elizabeth Blackburn, just chosen as a co-winner of the Nobel Prize in Physiology or Medicine.
Benet has published articles in nearly 500 scientific journals, written or edited seven books, and has the rights to 11 patents in pharmacokinetics, biopharmaceutics, drug delivery and pharmacodynamics. He is also one of the world's most highly cited pharmacologists, with his peer-reviewed papers cited more than 15,000 times.
In an interview with The Jerusalem Post during the one-day conference, the pharmacologist said he had visited Israel 13 times - first as a student in 1953. Since 1976, he has come to deliver lectures and has welcomed several Israeli post-doctoral students in his lab. In addition, his daughter is married to an Israeli-born lawyer who is the grandson of the late Israeli justice minister Haim Zadok. His own wife Carol Benet is a theater critic, and they have two children and six grandchildren.
AMONG THE Israeli post-docs he mentored was the late Prof. Abdullah Haj-Yihye, a leading clinical pharmacology expert at the School of Pharmacy who died a few months ago of a sudden illness at the age of 52. He came to UCSF in 1992 and remained with Benet for four years. A native of Taiba, Haj-Yihye was a resident of the Neve Shalom/Wahat al-Salam cooperative village of Israeli Jews and Arabs located between Jerusalem and Tel Aviv. Benet came specially to attend the conference despite a busy opening of the UCSF academic year to honor the memory of Haj-Yihye, whose wife and children attended. "Of 170 post-docs in my lab over the years, I would say Abdullah was the best. He was brilliant."
Benet, who has served the US Food and Drug Administration as a member of its science board and in other advisory positions, is also a board member or consultant to more than 20 pharmaceutical and biotechnology companies and has founded or co-founded several. He has also received numerous awards, including six honorary doctoral degrees. Benet serves on the board of non-profit drug companies, such as one that is developing a drug against leishmaniasis, the tropical disease spread by sandflies in tropical and subtropical countries and affects as many as 12 million people. Other products made by such companies are affordable contraceptives. "Poor women can get an intrauterine device for $10 that will prevent them from getting pregnant for seven years," said Benet. "The company was funded by an anonymous US donor."
The professor said that 15 years ago, the UCSF School of Pharmacy made the same step of switching to multidisciplinary teams and brainstorming as HU's is doing now. "We have combined specialists in bioengineering, pharmacogenetics, drug delivery, biomathematics and others. It is very successful, and I highly recommend this formula. Now it is part of one's job to get together, walk to the next-door office and talk to others."
The same scheme has been adopted all over the US, but European researchers and schools balk at the arrangement. "Most European universities don't like the approach. They are too insular. When European graduate students come to my lab, I tell them they have to interact."
A dozen post-docs currently work in his lab. Asked whether they are better than those of decades ago, Benet says they are definitely more skilled and knowledgeable; about half of them are women." It's worthwhile for them to study pharmacology as "even when pharmaceutical companies contract due to the economic situation, graduates get gobbled up and make good livings."
JEWS USED to be overrepresented as scientific researchers on campus, said Benet, but many have been replaced by Chinese, Japanese, Koreans, Indians and others from Asia. It is difficult to get admission. "There are still some Jews, but it seems most of them go into business," he commented. His own Jewish clan arrived from Lithuania in 1879. Benet received his BA in English literature and did his bachelor's of science at the University of Michigan ("I wanted to be an English professor," he disclosed) and his doctorate at UCSF.
But his interest in being a lecturer in English dissipated, as his family owned some small pharmaceutical companies, including Dara Products, which made hypoallergenic products. "I didn't want to run the company though," he recalled. Benet set up four small drug companies of his own; two of them, Limerick Biopharma and the Hurel Corporation, are still in existence. One makes microfluids that mimic the gut and liver so candidate drugs can be run through the system to see how they would affect mice, rabbis, dogs, monkeys and humans. Anti-vivisectionist groups like PETA, he said, "love me because such systems can reduce the use of animal experimentation."
A major trend in his field is pharmacogenomics, which involves the customization of drugs for patients so they get the right type and amount. "That's where the big advances will be. We will be able to know which drugs are toxic to a specific patient and which are not."
The FDA, with which Benet has professional ties, has been criticized for approving drugs too quickly, before all possible side effects and dangers can be assessed. He noted that he served on a panel that a year ago released a critical report of the FDA. "But I am also a supporter of the institution. There is always criticism that you are releasing drugs too early and some prove to be toxic, while others complain that you approve them too late and people are dying without it."
Asked about criticism that the pharmaceutical industry sometimes turns health problems into "official diseases" that "must" be treated by drugs - a phenomenon called 'medicalization' - Benet says there is some truth to this. "But in general, people live much longer today - and many of them live well. Longer lifespan with adequate health is a major advance and largely due to medications, which can even allow a 90-year-old with chronic heart failure to walk around." However, he agrees that potential profits can influence drug companies to issue expensive medications - such as those for psychiatric illnesses - that are no more effective than the old ones.
He continues to be shocked by the lack of universal health coverage for all Americans. "I am strongly in favor of health reform. It's unbelievable that in the richest country in the world, the needy can't get decent medical care. And when uninsured people, even middle class, get sick, all their savings are wiped out."
Nanotechnology has considerable potential, but he is not sure how it will pan out. "It is not the only answer to diseases. Technologies come, and doctors get excited, but then they go on to something else. We still don't know what the mechanisms are. For drug delivery to work, you have to know where you want to go. Many times, you don't know. The pharmaceutical industry has spent much money on hypothetical mechanisms, such as cellular systems in the lab that were all wrong. They gave it to people, and it didn't work."
Benet also urges stronger supervision of clinical trials. "That is fault of the universities that are not monitoring properly what their faculties are doing; but at UCSF, we are very rigorous. In many universities, people are listed on journal papers as having done research even though they were not involved at all. The situation is being cleaned up gradually. At my university, you can't hold on to any of the consultation fees you earn. You must give them to the university. You get a state salary plus a supplement based on your reputation and experience."
Benet is "not a big fan of complementary medicine," but he recognizes that many patients feel better even though the treatments have no proven therapeutic result - the placebo effect. But going only for complementary medicine is dangerous, and people make bad choices." However, it is fortunate, he added, that US patients going to an MD are required to report to them on any complementary treatments and supplements they take, as they can have harmful interactions with medications.
Finally, Benet said Israel is a perfect lab for testing drugs, as there are a huge variety of ethnic groups and skilled doctors. "Israel is world class in a variety of pharmacological fields including drug-delivery systems. It is always fun to come here. In the late 1970s, I came to Israel and delivered in Tel Aviv hospitals a lecture for cardiologists on medications that treat irregular heart rhythm. I was surprised that nobody showed any interest. I asked why, and they said they didn't use these drugs at all, as certain ethnic groups had bad side effects. I went to Taiwan and delivered the same lecture, and everyone was interested. I asked if they ever use the medications, and the doctors said these were the only ones they prescribed and that they never saw side effects. We found that Ashkenazi Jews have a deficiency in an enzyme that produces harmful antibodies. This was one of the first indications of the need for pharmacogenomics."