Avital Sharir-Ivry explains quantum chemistry to me: “Chemical reactions also occur on the level of electrons,” she says while on lunch break. “My field was enzymes. When a small molecule enters a large enzyme, there’s a reaction. For example, something is broken up very quickly. This process follows theoretical quantum guidelines we can use, as I have, to build a computerized model that can show how the molecule will react.”
The lunch break is part of a workshop held by Science Abroad, which aims to make connections between Israeli scientists currently out of the country and present them with paths to return home and find meaningful work. Immunology and cancer research feature heavily in participants’ biographies. The workshop is hosted at the offices of the Pearl Cohen law firm – which handles Lemada, creators of Rummikub and other games – and sponsored by Delta and Teva.
Teva’s Nir Shapir takes a moment to ensure I understand what biosimilars are. All drugs cause a chemical reaction within the body of the patient. For example, people who suffer from malaria can take quinine to get better. Quinine is produced from the bark of the cinchona tree and destroys malaria pathogens.
An in-depth look will reveal that the working mechanism of quinine, used by Westerners since the 16th century, also has unique chemical aspects, but it is not a designed drug that requires profound knowledge of the individual patient, the mechanism of the illness, or the manner in which the active material needs to be introduced to the body. At least in theory, it’s a simple drug. If you’re in the tropics and suffer from malaria, you seek this tree and grind its bark into something one may digest, and you get better.
Cancer, however, is a complex array of diseases, each unique. Every one of them interacts with a specific person in a way that corresponds to his or her genetic heritage, upbringing and even habits.
Shapir draws for me a receptor inside a cell and an active component. “Let’s say that when the receptor catches the active component, I get a reaction,” he says, “and the patient simply doesn’t have the right shape of the active component. Perhaps his body produces it in a different shape. If that’s the case, we can’t get a useful reaction. Or perhaps the body of the patient produces too much of the material, and the reaction is much more powerful than we’d like it to be. Or perhaps the reaction is harmful and we’d like to stop it altogether by blocking the receptor with something else, so it would not happen.”
Such fine-tuning of the biological system isn’t actually novel; all drugs do that, even the humble quinine. But for the first time in human history, we are able to go so deeply into the working mechanism of the drugs we need to heal our own bodies. These are biological drugs, and to design them you need $1 billion, says Shmulik Hess, the chairman and founder of Science Abroad, who points out that sometimes you spend $1b. and, despite predictions, the drug doesn’t work as you expected.
“Herceptin is a biological drug,” Shapir explains. “It is used in breast cancer.”
What he does not say, because it’s terribly complex and requires deep scientific knowledge, is how the drug works. It connects to cells on a molecular level, it is in conversation with a specific gene (ERBB2), and this conversation flashes other genes on and off, as, it turns out, genes are not like a cake recipe that predetermines everything about you; they are possibilities, and can go on and off based on various factors. In films such as Gattaca (1997), genes are presented as secret tell-all cards that, essentially, seal one’s fate. This is not exactly how genes function.
Herceptin is a biological drug, and, like Rummikub, it has a maker – Genetech. Like the game, it is also protected by a patent, which highlights the relations between new wonder drugs and intellectual property. It takes $1b. and the collective efforts of very bright, highly trained people like Shapir, Hess and Sharir-Ivry to create it. An American woman suffering from breast cancer will pay roughly $70,000 for a full course of Herceptin treatment.
According to a press release issued by Science Abroad, the average scientist contributes to Israel’s gross domestic product five times more than any other average citizen. It claims that each scientist who, as Sharir-Ivry does now, works in Canada or any other place outside the country costs Israel NIS 2.5 million.
This is all very humbling when I consider that two lawyers, one reporter, a vet and a school teacher together are needed to rival even one of the people around me in GDP terms. Incidentally, Iran, China and India all operate substantial programs to bring their own scientists back home from the science halls of the West, mainly from the US, with similar considerations.
The patent for Herceptin will expire in 20 years, Shapir tells me, and this is when a company, for example Teva, can carve out a chunk of the market by offering a biosimilar. A biological drug that will instruct the proteins and the genes and the neuron pathways of female breast cancer patients with ERBB2 to do what they would have done under the influence of Herceptin. This is what Shapir is in charge of. He is Teva’s vice president of biologics and biosimilars R&D. Plainly put, he is one of the people Teva trusts to give it an edge in fighting off its rivals in the market.
According to Teva one out of five prescription drugs sold in Israel is made by them; one in seven in the US; and one in eight in the UK.
It should be noted that biosimilars are not at all like producing Triumph motorcycles in India. People don’t usually need to ride a motorcycle to stay alive, yet the current structure of the global drug market means that cheaper biological drugs are a must for a huge number of people in India, China and Africa, not to mention Americans who can’t spend $70,000, even to stay alive.
IN 2017, Teva fired 1,200 Israeli workers [they employed 6,200]. At the time, the evening news featured workers protesting outside closed factories, and angry editorials pointed out that Teva got significant tax breaks from the government to encourage it to maintain production in Israel and generate jobs – the same jobs it was now terminating. Doing the math, I realize that was around the time Shapir joined Teva.
Teva’s position, as expressed by Mati Gill, head of government affairs, corporate and international market, is that the cooperation with Science Abroad is done with the goal of “locating experienced and skilled talents that will enrich Israeli biopharma industries, which are a critical component to the growth of the Israeli economy.” He adds, “Teva, which sees its home in Israel, depends on [these two factors].”
He stresses that Teva isn’t focused solely on returning Israelis home so they can work for Teva. From Teva’s perspective, it’s always better for talent to come home and contribute to the industry. When the tide comes in, all the boats rise.
The trouble with biotech, explains Hess, is that you can’t create a security-derived application with seven guys working from a rented flat living on pizza. You need $1b., sterile factories and labs, and large teams of highly trained people. Even then, you may not make it, as the drug might react in ways different from what you expected.
This is why, while Israel is a global powerhouse in hi-tech innovation, it isn’t the first place to go to when people are considering biotech, at least not yet. Hess gives the example of stem cell research: a field once pioneered by Israelis is now almost without Israeli involvement.
However, unlike Israeli hi-tech talents who, he says, “rarely wish to return from the ‘fleshpots of Egypt,’” Israeli talents in biotech do want to come back. Their problem? Well, they usually don’t have $1b. to finance their own research and they spent the last 15 years in a lab. One of the functions of this workshop is simply to allow scientists to get to know the industry and what paths it might have to offer them.
“It’s actually an upside-down pyramid,” Hess explains. “Almost everything important came from what we call curiosity-derived science – just allowing people to research what they find interesting. Yet bear in mind there’s a 20 to 30 year gap between the publication of the academic paper and the commercial drug it eventually led to.”
He adds that in large and established companies, Bell Labs for example, they might even hire talent to just be a part of the discussion without a specific job in mind. Yet that sort of freedom is getting harder and harder to find, as universities face reduced funding and layoffs.
“To get scientific training and skills is like getting a driver’s license,” he says. “You can go anywhere. It doesn’t matter if you drive this car or that car, what matters is what you do with it. We want them to consider using their driver’s license in other ways besides pure research.”
According to its press release, Science Abroad was able to assist the return of 700 Israeli scientists and maintain social contact with nearly 3,000, making it a logical starting point to anyone in the industry seeking Israeli talent as well as a comfortable connection to Israelis who don’t wish to become full-time, lifelong skilled immigrants.
I RETURN to the buffet table and seek out Elad Eliahoo, who pioneered a novel way to castrate cats without requiring an operation.
Cats are among the most destructive species on the planet. This is not their fault; they’re furry predators humans favor and provide food and shelter to, and in warm countries, like Israel, street cats breed into fantastic figures and eat anything they can catch – whether mice or rare birds.
Eliahoo was able to design a virus that carries an active component that causes the cat’s immune system to attack sex hormones, which means cats who get the shot do not go into heat and do not reproduce. Not only that, he adds, but the virus affects only the cat it was injected into and is highly unlikely to travel to other species.
This blows my mind. Scientists, like Eliahoo, are currently able to hijack an immune system, give it commands, and design a delivery system for it. In theory, one could design such a virus to sterilize a specific community or to kick in if cells even begin to signal they are on the way to becoming a cancer cell.
Eliahoo explains that the shot is cheaper and easier to use than capturing cats, operating on them, and releasing them in the same spot, but my mind is at a different point by now. I’m thinking about the cat-sterilizing virus getting out of hand and wiping out other species, such as humans.
Eliahoo gives me a highly patient look and explains that “the virus is not going to complete its life cycle, because we removed huge chunks of its genetic sequence so it can’t reproduce. To regain these chunks, the virus will have to find another virus and take them off it, which is so unlikely to be almost nil.”
I use the classic line spoken by Jeff Goldblum in Jurassic Park (1993): “Life finds a way.” Eliahoo thinks about that for a moment, and then shares with me that vaccines against rabies are already given to feral animals using just such a mechanism.