By Sara Rimer – Photos by Cydney Scott
Original story published at BU RESEARCH
Less than a decade ago, thee-cigarette was an obscure product marketed as a safe, tobacco-free alternative to conventional cigarettes by a single company in China. Seven years ago, the electronic nicotine delivery device entered the US market. Today, health officials, policy makers, and researchers are all scrambling to keep up with a rapidly expanding, wildly controversial, and largely unregulated $3 billion global industry that has, at last count, 466 brands, 7,764 flavors (bubblegum, cherry crush, bacon, java jolt, menthol), and slick, youth-oriented Big Tobacco marketing designed to create the perception that e-cigarettes are not only safe, but cool.
With the public health community sharply divided over the potential benefit and harm of the popular device—and with conclusive scientific evidence in short supply—the World Health Organization (WHO) released a report in August 2014 that raised serious questions about the health impact of e-cigarettes and called for a ban on indoor use and sales to minors. The report expressed “grave concern” over the growing role of multinational tobacco companies, warning that they could turn e-cigarettes into a gateway for a new generation of smokers at a time when a decades-long public health campaign has successfully reduced smoking rates in the US and other developed countries.
Also in August 2014, the Centers for Disease Control (CDC) reported that more than a quarter million youth who had never smoked a cigarette used e-cigarettes in 2013, three times the number of users since 2011. The Food and Drug Administration (FDA) proposed bringing e-cigarettes under its control alongside tobacco in the spring of 2014, but that proposal is enmeshed in debate and lawsuits. Dozens of states and cities across the country, including Boston, have already banned the use of e-cigarettes indoors.
At Boston University, Avrum Spira (ENG’02), a pulmonary care physician and School of Medicine professor of medicine and pathology and bioinformatics, and College of Engineering professor of systems engineering, who studies genomics and lung cancer, was one of the first scientists to receive funding from the FDA to investigate the health effects of e-cigarettes. “In theory—and how they’re marketed—e-cigarettes are a safer product because they don’t have tobacco, which has known carcinogens,” Spira says. “The question is: does safer mean safe?”
Across BU’s Medical Campus from Spira, Michael Siegel, a physician and professor of community health sciences at the School of Public Health, has emerged as perhaps the country’s most high-profile public health advocate for e-cigarettes. Siegel, who is not currently researching e-cigarettes, says he believes that the device could potentially help large numbers of smokers quit, or drastically decrease, a habit that is the leading cause of preventable deaths in the US. He points out that despite all the existing smoking cessation products on the market, only a small fraction of cigarette smokers manage to quit. Only 4 to 7 percent break the habit without some nicotine replacement or medication, according to the American Cancer Society. At the same time, Siegel says, more research is needed on the health effects of e-cigarettes as well as their effectiveness in helping people quit smoking.
Arum Spira is a Boston University School of Medicine professor of medicine and pathology and bioinformatics and College of Engineering professor of systems engineering, the Alexander Graham Bell Professor of Healthcare Entrepreneurship, and chief of the Division of Computational Biomedicine. He is a pulmonologist at Boston Medical Center. With funding from the National Institutes of Health and, more recently, the Department of Defense, he has been working to develop molecular tests for early detection of lung cancer. Spira talked with BU Research about his research into the health effects of e-cigarettes, which is being funded by the FDA.
- BU Research: You’re a pulmonary researcher who has done groundbreaking work on early-stage lung cancer detection. You’re also a pulmonary care physician and you’ve spent years treating patients with advanced lung cancer who had been heavy smokers. What are your concerns about e-cigarettes?
- Spira: It took decades after cigarettes were introduced to sort out the health effects, which were devastating. Many people got addicted and they couldn’t quit once the health effects became clear. The devastation is truly hard to imagine; according to the 2014 Surgeon General’s report, more than 20 million deaths have been attributed to smoking in the US since the 1960s. The tobacco companies have recognized for many years that their product is hurting their customers, which also impacts their sales. So they have recently started to develop “safer” products. There is a lot of controversy around this. How do we know a “safer” product is really safer?
- But before the big tobacco companies got involved, weren’t e-cigarettes introduced and produced by independent companies as a way to get a nicotine hit without the tobacco and carcinogenic tar—as a safe alternative to cigarettes?
- Yes, we could say that e-cigarette products have exploded in the marketplace, specifically in terms of brands, delivery devices, flavors, nicotine concentrations, as well as the delivery liquids. It’s a complicated, fascinating, and rapidly moving space. There are currently a myriad of ingredients that can be combined in different ways to produce the vapor. This does present a challenge for researchers looking to identify the agents that are harmful, as each e-cigarette product is potentially different than the next. The FDA is trying to get a handle on standardization and potential risks of e-cigarette products by funding groups like ours to develop systems to rapidly assess these factors. But the research community is still scrambling to keep up with the rapid and unanticipated changes in this field.
- Can you explain how e-cigarettes work?
- E-cigarettes are a device that delivers nicotine—which is one of the addictive substances in cigarettes—without any actual tobacco, or tar. Tar has hundreds of known carcinogens. E-cigarettes have a battery-powered cartridge that heats a liquid containing nicotine and potentially a flavoring, which creates an aerosol that is inhaled. The e-cigarette community refers to this as “vaping,” where traditionally we’d call it “smoking.” Now, when you heat a liquid, it changes the chemical composition of that liquid and additional chemicals can form (e.g., formaldehyde, acetaldehyde, and acrolein), which are then inhaled by the user. The question is: are those other chemicals harmful or not?
- What do you think about the public health argument Professor Michael Siegel (of the School of Public Health) and others make, that e-cigarettes are an important tool for helping cigarette smokers quit who might not otherwise be able to?
- I understand his perspective and don’t entirely disagree. If there’s a smoker who can’t quit but who can use this product instead, that has a health benefit. This is almost certainly better than smoking traditional tobacco cigarettes. If this is a vehicle for quitting or a better alternative to traditional cigarettes, it could have a huge public health benefit. There are 45 million current smokers, adults in the US, who are unable or unwilling to quit. It’s still a major public health problem. The other side of the debate is that this normalizes smoking behavior, that it’s an entry point for younger people. A 15-year-old, an 18-year-old, says, “Okay, this is safe product,” and gets addicted and it becomes a gateway to other products, including traditional cigarettes.
What does your research tell us about the health effects of e-cigarettes?
Our group was one of the first, in collaboration with Dr. Steve Dubinett (a pulmonologist at UCLA) to get funding from the FDA to study the health consequences of vaping. Our approach to evaluating e-cigarettes is based on what we’ve done with tobacco cigarettes, where we’ve developed genomic signals of exposure and, to take that a step further, signals of disease risk (e.g., lung cancer and chronic obstructive pulmonary disease, or COPD).The question is: Does exposure to e-cigarettes create the same genomic changes in the airway as tobacco cigarettes do? Our prior work, over the past decade, has characterized a large number of genomic changes that traditional cigarette smoke causes in epithelial cells that line the upper airway (e.g., the windpipe) and has identified a smaller subset of changes that are associated with development of lung cancer and/or COPD among smokers. We are currently evaluating whether e-cigarettes produce similar gene expression changes as traditional cigarettes. In addition, we can correlate these genomic signatures to signatures of disease risk and begin to assess the chronic potential harmful impact of these products.We decided to do our research in two phases. We started off with cells in culture. We took human bronchial epithelial cells that contained some mutations found in smokers at risk of lung cancer and cultured them with media that contains everything that comes out of an e-cigarette. The idea is that you’re “smoking” the cells.We found that the electronic cigarette was able to cause cells to become more cancer-like—they grew more quickly than a cell should be able to. That is one of the things that cancer cells do. That is the only thing we found—that it did change their growth rate significantly, more than smoking nothing and similar to smoking regular tobacco. That raised concerns on our end. Then we looked at the cells’ genome and found that many of the same genes turned off and on by tobacco cigarette smoke are being turned on and off by e-cigarettes.And you’re now in Phase Two of your study? Can you tell us about that?Our ultimate objective in Phase Two is to take people who smoke tobacco cigarettes, have them switch to e-cigarettes for at least two months, and sample the cells in their windpipe and their nose both before and after they switch. We would then perform genomic profiling on these samples. This entails measuring the activity of all 20,000 genes in your cells, which we can do in 24 to 48 hours. This produces a large amount data, so this is where computation comes in.We are able to compile all of the data for all of the people we profiled and ask general questions, such as: when individuals switch to e-cigarettes, do their gene expression patterns or profiles resemble that of a former smoker? This would suggest that the product is potentially safer. Alternatively, does your genetic profile continue to look abnormal? And in that case, we would argue that e-cigarettes aren’t necessarily safer.With regard to disease, some smokers’ genes turn on differently and that puts them at risk for cancer. So we can also look and see whether electronic cigarette exposure produces similar genomic changes that are associated with lung cancer.Should e-cigarette users be concerned? Should they stop vaping?We’re not saying that e-cigarettes cause cancer. We can’t say that based on this data. What we’re saying is that we have evidence from cells in culture that e-cigarettes could have effects that are similar to tobacco smoking and that many more studies are needed before we can say this is a much safer product. That’s where this fits into the whole public health debate. The FDA wants the academic community to come to the table with new approaches. That is what we responded to. The FDA has made a significant investment in our group and many other groups across the country to help study this in far greater depth. While it will likely take years via longitudinal studies to be absolutely certain of the safety of this new product, we’re in the process of getting more data in the short term that will give us some more insight into the potential risks of e-cigarettes, so that potential users have that information.
- What about the public health history in terms of cigarette smoking and the lessons learned there?
- We don’t want to go down the road we did with cigarette smoking. It took 20, 30 years until the epidemiologic data came out convincingly that cigarettes cause cancer and other diseases. For many people, it was too late, as they were unable to quit and/or had already developed disease.The genomic technology we have today—these approaches weren’t available back then. It took long-term epidemiologic data before risks of exposure became clear.We are in a new era of science and technology and medicine where we can do new types of translational studies. This type of science can potentially be done very quickly. We’re not there yet and we won’t be in a few months. Maybe in a couple years…but it need not be decades. We don’t have to repeat the past. More science needs to be done as quickly as possible. We need to take a very careful look at this product and come to some preliminary conclusions. It’s going to be very difficult to put the genie back in the bottle—the longer people use it, the more difficult it becomes to stop.
- Why do you care so much about this research?
- My passion is to care for patients with diseases. An ounce of prevention is worth a pound of cure. Most people start smoking when they’re young. I take care of them many years later when they become a patient. I wish I could go back and stop them from starting smoking. I feel like this is my opportunity with a different product to perhaps prevent young folks from engaging in a behavior that could be harmful—so at least they’re armed with information. E-cigarettes are, in theory, a safer product. They don’t have a lot of the components found in tobacco. It’s just—they may be safer, but they may not be safe. We need to clarify and I think it’s important the public have that information. Even if e-cigarettes are not as bad as tobacco, it’s important that we know what their health impacts are.When I became a lung doctor, I was seeing a huge population of smokers who were getting diagnosed with lung cancer at this institution at an advanced stage where I couldn’t offer them any effective treatment. We need to detect this disease earlier and prevent it. Once you’re diagnosed with lung cancer, your survival rate is very poor.
- What do you think about people who smoke cigarettes?
- I’m okay with someone eating wrong, not exercising, smoking—as long as they know about the consequences of that behavior. I take care of a lot of people who smoke. A lot of them started when they didn’t know it was bad to smoke. Smoking was a cultural phenomenon. People didn’t know the health effects—and it’s addictive. Later you can say, “Now we know,” but if you’re doing an addictive behavior for 20, 30 years, it’s really hard to stop.I don’t judge smoking at all. I take care of patients unable to quit. That’s why I see Siegel’s argument. I know how hard it is to quit. Even some patients with lung cancer still can’t quit.