Co-discovered photodynamic anti-cancer and ophthalmology drugs, co-founder of the company QLT Inc.
"The most important thing: Never shut off your options. You never know what the next year is going to bring. If you leave your options open, then when something happens you know, ‘That’s where I want to go.’ And you do it! Never box yourself in."
In 1986 Julia Levy was giving a talk to some doctors in Waterloo, Ontario about her work on new light-activated drugs. A few years before, she had formed a spinoff company called Quadra Logic Technologies (now QLT Inc.) to commercialize her university research. The doctors were trying these drugs on cancer patients and they were very upset because Johnson & Johnson, another drug company, was closing down their Photofrin research program. Photofrin was one of the new photodynamic drugs, and it appeared to be effective against cancer. Many people were being helped by this technology, but soon they would not be able to get the drug. “It was a very upsetting experience for me,” says Levy, who until that point had worked on these drugs only in a laboratory. “For the first time, I became aware that we were talking about real patients being treated for real cancer.”
That night, on the plane flying back to Vancouver, Levy began thinking: We’re in the business of photodynamic therapy. We should get into this at the first level and we should perhaps start making Photofrin, at least for Canadian investigators. She sat pondering this all the way home and became very excited. When she got off the plane she immediately called her business partner, Jim Miller, and said, “We’ve got to do something.” She just wanted to help cancer sufferers. “Let’s make the product. We know how to make it.” But Miller surprised her. “We’ll take over the company,” he said, meaning the Johnson & Johnson subsidiary that was making Photofrin. They made a deal with the pharmaceutical company American Cyanamid, raised $15 million and took over the subsidiary. It was a major turning point for QLT and for Levy.
“Being in business — in commercial science — focuses your science,” says Levy. “The big difference between university and commercial science is not the quality of the research; it’s your awareness that as you move a drug forward towards getting it into a patient it’s going to cost you a fortune.” Getting a new drug treatment perfected costs about 10 times as much as inventing it in the first place, and therefore you cannot afford to make mistakes. Maybe that’s why it suits Levy’s personality. She likes to do things right the first time and she hates retracing her steps in any way. She says, “You can’t afford too many goofs when a single experiment costs $50,000.”
In April 1993 the Canadian government approved Photofrin for the treatment of bladder cancer. It can also be used to treat cancers of the skin, lung, stomach and cervix. In 1995 QLT received approval to treat esophageal cancer in Canada and the United States, and it obtained very broad approval in Japan to treat a wide variety of cancers.
Throughout the 1990s QLT embarked on many new research programs to treat other diseases using photodynamic therapies. It looked at autoimmune diseases such as arthritis, psoriasis (a skin disease) and multiple sclerosis. “It’s way beyond cancer,” says Levy, excited about the potential to cure other diseases with this new drug.
By far QLT’s biggest success is Visudyne, a photodynamic drug for the treatment of the eye disease called macular degeneration. Based on the active ingredient in Photofrin (a benzoporphyrin derivative that goes through a chemical change when exposed to a particular wavelength of light), Visudyne is QLT’s biggest biotechnology product in terms of sales (about a half billion U.S. dollars in 2004). It is the most lucrative drug product ever launched in the history of eye medicine. “We got lucky,” says Levy. “You can’t do it just with luck, but luck helps.”
The chain of “lucky” events begins in the late 1980s, around the time Levy was investigating how to cure cancer with photodynamic therapy. Her mother began losing her vision from age-related macular degeneration (AMD). Levy had never heard of AMD, so she decided to read up on it. She discovered that, worldwide, about half a million people get the “wet form” of AMD every year — the kind that her mother had. It’s the leading cause of blindness in people over the age of 55.
Shortly after learning about AMD, Levy happened to be at a conference on photodynamic therapy where, for the first time, she heard a doctor talking about how the eye was the perfect organ for treatment by photodynamic therapy. Unlike lungs and bladders, where doctors have to thread in a long fibre optic cable to treat a tumour with light, with an eye they can simply shine the light directly in. They don’t need much fancy equipment. The doctor listed many eye abnormalities and diseases that might be treated by photodynamic drugs. Even at this point, the “light did not go on” for Levy. She knew QLT did not have any money for eye research at that time.
A few months later she was at Harvard University in Cambridge, Massachusetts, to meet scientists who were conducting trials of QLT drugs on patients with skin cancer. Levy had only dropped in to see how things were going, but she met an ophthalmologist there named Ursula Schmidt, who had been going to the skin cancer research lab to get the empty bags of QLT photodynamic drug out of the garbage bins; she would take them back to her lab and squeeze out the last drops for use in experiments on animals with eye diseases.
“As it turned out, we had just raised some new money in Vancouver and we were looking for research projects,” says Levy. By then it was too late for her mom, but Levy decided that QLT should work on a photodynamic drug for eye disease.
Within five years, by 1995, QLT had a drug ready to try on a human patient. Even that first crude drug gave a positive effect. The rapid development of Visudyne was very unusual. Most drugs take more than 10 years of testing before they are considered safe to use on humans. Visudyne went to market faster because it satisfied a great need.
During World War II, a few years after Julia Levy was born in the Asian city-state of Singapore, her father was captured by the Japanese and put into a prisoner-of-war camp. Just before this, her mother had escaped to Canada with Julia and another daughter. After the war her father rejoined his wife and children in Vancouver, but his experiences as a prisoner left him a broken man and he was not able to support the family. This taught Levy to be self-sufficient and that a woman should never get married just to have someone to look after her.
Even as a little girl Levy was interested in biology, though she always felt she would grow up to be a piano teacher. On weekends she would return home from Queen’s Hall boarding school in Vancouver and go for walks with her mother in the woods near their house. Their dog would romp along, collecting stray mutts that would stay at their house for several days. Sometimes Julia would take a sieve and a jar on the walks to bring back frogs’ eggs; she and her sister would grow tadpoles in wash basins in the basement.
Levy enjoyed mathematics in high school and in grade 11 had a particularly inspiring biology teacher, a woman. After obtaining a bachelor of arts (BA) degree in biology from the University of British Columbia in Vancouver and a doctorate (PhD) in experimental pathology at University College in London, England, Levy became a professor of microbiology at ubc. In the 1980s she co-founded QLT.
By 2004 QLT had become a world leader in sales of drugs that treat macular degeneration. It was one of the most successful high-tech companies in Canada. When asked how it feels to create such extraordinary wealth, Dr. Levy says, “Well, when I look at it I think ... me?” She gets a look of wonder on her face but quickly adds, “And a lot of other people — you can’t do it alone.”
Microbiologists research such areas as bacteria, fungi, viruses, tissues, cells, pharmaceuticals and plant or animal toxins. Julia Levy is a microbiologist and immunologist, someone who studies the human immune system, the collection of molecules and cells that help the body fight off disease. Together with colleagues from UBC she develops drugs that are unique because they are photosensitive, which means that upon being exposed to light they change in some way that makes them toxic to cells. This photodynamic therapy can be used to treat lung cancer and other diseases such as AMD.
AMD affects a very tiny part of the eye called the macula, the “business part of the eye,” as Levy calls it. The eye is like a camera, with a lens at the front and a sort of “film” at the back called the retina. The retina’s job is to convert light into nerve signals for the brain to turn into images. The macula is just a few square millimetres near the middle of the retina, but it has millions and millions of finely tuned light receptor cells — many more per unit area than the rest of the retinal surface. It’s the part of the eye where we turn our focus to read and write, to draw or work with our hands, to watch TV, to prepare and eat food or to recognize faces, among many other activities that require the discrimination of fine detail.
In people with AMD, microscopic blood vessels grow abnormally and invade one of the membranes at the back of the retina, where the vessels start leaking. “The macula is the only part of your body where if even one micron (one-millionth of a metre) of it is hurt, your vision is damaged,” says Levy. Most other parts of your body can sustain damage in large chunks and work just fine, but not the macula. It’s one of the most incredible parts of the body.
For people with AMD, the centre of their vision is blurred or distorted or things appear odd in size or shape. For instance, things that are normally straight, such as doorways or telephone poles, might seem bent or crooked. As the disease gets worse, a blank patch or dark spot forms in the centre of their sight. This makes activities like reading, writing and recognizing small objects or faces very difficult. Nobody knows why AMD occurs, but there seems to be a genetic component; it runs in families. Europeans are more prone to get it than Asians or Africans. It is also related to age; about half of people over 85 have it.
1. Photodynamic drug Visudyne injected into the bloodstream through the patient’s arm.
2. Low density lipoproteins (LDL) are large molecules that carry fatty material in blood. They form a chemical complex with the drug to take it to all parts of the body.
3. The verteporfin molecule, the active ingredient of Visudyne developed by Levy and other scientists at QLT. This molecule changes when exposed to red light.
4. The drug accumulates in the abnormal blood vessels of the diseased macula, part of the retina at the back of the eye, where new blood vessels are growing improperly, causing the disease. The abnormal vessels attract and absorb the LDL-Visudyne complex.
5. Because new blood vessel cells grow faster than normal cells, they invade one of the membranes of the retina and start leaking. This is the cause of one form of macular degeneration disease. Their faster growth rate also makes them take up verteporfin about 10 times more quickly than normal cells.
6. About 10 or 15 minutes after the injection, doctors shine cool red laser diode light into the eye for about 90 seconds. The light has a wavelength of 690 nanometres, which is the optimum shade of red for activating the verteporfin, creating free oxygen molecules. The oxygen reacts with the abnormal blood vessel cells and effectively “burns” them up.
7. The abnormal vessels are destroyed.
All the science for Visudyne is done in Vancouver, but the active ingredient is made in Edmonton, Alberta, and then modified in Japan to make it soluble. Finally, the product is bottled and labelled in the United States. More of this process will soon be moving to Vancouver.
Levy says that although researchers know a lot about the biology of cancer cells, how cancer cells develop is still one of the biggest mysteries around.
Wikipedia entry on Macular Degeneration
Julia Levy’s web page at QLT Inc.
So You Want to Be an Immunologist
The whole area of clinical biology and biotechnology is expanding rapidly and will become a significant part of our future. Not long ago, if you were a biologist you had only one real option: teaching. Now there are countless career opportunities: clinical research, regulatory work for government and industry, marketing, manufacturing and quality control in biotechnology, chemical, pharmaceutical, food, health care, resource, environmental, forestry, agriculture and consulting companies. There are more courses being taught, as well, in universities and colleges. A strong scientific base with a university degree is now a prerequisite even for the marketing jobs at biotechnology companies and in other high-tech industries. Salaries start at about $30,000 a year and can go up into six figures. However, Levy says, “I’ve never found money to be a compelling reason to do anything.”
Typical training required for a degree in biotechnology is a four-year bachelor’s degree, followed by three to five years of post-graduate work leading to a master’s or doctorate. Jobs are available with any of these levels of university education. “Above all, you need to have a love of science and a curiosity for the subject,” says Levy.
There’s no such thing as a typical day for Julia Levy. Some days are spent in meetings with other companies, others reading scientific literature, still others meeting her qlt colleagues to work out business strategies. Levy likes everything about her job except the travelling and talking to investors.