A pause for reflection

I mentioned before that I often have my posts mostly written in my head before I ever sit down to type them out. And indeed, though I hadn't had a chance to actually sit at a computer yet, I had a science post all planned for today, based on an article I ran across last week. I think that will wait for tomorrow, though, after reading this post over at Terra Sigillata, where Abel writes about the sudden death of a 23-year-old brother of a former lab intern from a staph infection.

I sometimes get asked why I "waste my time" studying infectious disease, when they don't cause nearly the mortality burden that "chronic" diseases do here in the U.S. And yes, diseases such as cancer and cardiovascular disease cause more deaths in the U.S. than infections do. Yes, these deaths, too, can be sudden and unexpected, and of course, are frequently tragic for the loved ones involved. But for me, there is an added dimension to infectious diseases that make them both frightening (in their often sudden onset, potential transmission to others, and interaction with the host) as well as fascinating to investigate. Abel's story has an added dimension, in that the brother's cancer treatment left him immunocompromised, and likely contributed to his death from infection--but even healthy people can quickly succumb to infectious disease, and as Abel mentions, anything we do seems inadequate. Not enough money, not enough research, not enough compassion to go around.

Abel notes:

What still amazes me is how quickly an otherwise healthy person who is transiently immunosuppressed can die so precipitously from a bacterial infection. It makes me wonder why Big Pharma hasn't more aggressively tried to tackle this problem, or whether there are challenges that preclude them from doing so. It makes me want to take a tutorial from Tara or Revere or someone at our School of Public Health to learn more, and maybe even get into ID (infectious diseases, not intelligent design) research.

I can't speak much on the Big Pharma issue, but Abel's post did make me stop for just a moment. Obviously, I work on infectious diseases. I work on pathogens that aren't necessarily the leading causes of mortality in this country, but ones that I find interesting for a number of reasons. To do this, I have to try to justify my research to agencies with limited money, working to show why my species are worthy of a monetary investment--and I have to do this without eloquent and touching stories like Abel's.

However, this doesn't mean that I, personally, have to be quite as unfeeling. I my freezer, I have around 100 isolates from invasive disease caused by Streptococcus agalactiae. While it is easy just to think of them as numbers and strains, they are much more than that. They are one person's horrible pain from a destructive skin infection, or a wound that just wouldn't heal due to complications from diabetes, or another person's pain from the loss of their newborn child (since group B streptococcus is a major cause of neonatal meningitis and death). Each pathogenic strain often represents a life changed, or a life lost. And though these are discussed in the scientific literature in dry, clinical terms, that doesn't mean that those of us who do the research, or write the papers, aren't touched on some level by the real patients who've suffered--or even died--from the pathogen we research.

It's easy for critics to be cynical about scientists and doctors, and our motives for doing what we do. Clearly, we need to make a living, and that living depends on being paid for our work. And undoubtedly, there are people who abuse their positions as a scientist or a medical practitioner. But there are also those who are simply touched by the suffering brought on by various diseases, and want to do some small part to alleviate that suffering, even if we know it won't stem that feeling of inadequacy in the face of so much human illness.

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You have to do what you love. Sure, you could have gone into chronic disease research and would have been more financially secure grantwise, but would you have been as happy? Would a bunch of cancer cells have made your ganglia dance like your isolates do?

A few weeks ago, one of the department's programs were being audited. I remember walking by the conference room where all the accountants were poring over reams of accounting records and I thought, "wow, how boring must that be?" Then I went back to my desk and started poring through reams of hospital discharge records. Man, they don't know what they're missing.

What a lovely and thoughtful post, Tara. We all do what we love and I feel that much of it has been molded by experiences we've had before school and then during our careers. As this episode has taught me, one that happens to dozens of people daily, is that no matter how good I am at coming up with the next cancer drug, it must be able to distinguish between proliferating cancer cells and proliferating normal cells. Otherwise, I've got to start working on antibacterial drugs, or modalities that sequester endotoxin and/or cytokines resulting from bacterial cell lysis. There is always more to work on, and always ways for us lab folks to think about minimizing human suffering.

I think that we've been lulled into a possibly false sense of security by the success of antibiotics. We've forgotten what a scourge bacterial diseases have been in the past, and that the reason that "slow" illnesses such as cancer, heart disease, and neurodegenerative disease are such current concerns is that more of us survive long enough to have to worry about them. I think we also tend to forget how thin the line of defense is. Bacteria evolve faster than almost anything on the planet. There are already a few strains that are resistant to almost everything we can throw at them, and these are often the ones that are at fault when somebody dies of "complications" after an apparently successful surgery. And even antibiotic-sensitive strains can take you out if they get the jump on you. Jim Henson died of a group A strep infection.

Although there is some work being done on antibiotics in Big Pharm, it is not a big focus. Part of this is just dollars and cents. Antibiotic drugs have a problem: they actually cure people. You take the drug for a few weeks and you're done. What is more, the older antibiotics are cheap and effective, so there is not much market for a new, expensive antibiotic. You don't need a new one until the old ones stop working. The worry is that that could happen very fast, if some antibiotic resistant strain goes epidemic, and drug discovery takes years. A lot of people could die in the meantime.

The other part of the problem is that antibiotic drug discovery turns out to be very difficult and expensive. Brute-force chemical library screening and rational drug design approaches that have worked well for other diseases have been less successful for antibiotics. Most of the antibiotics we use are still based on natural products discovered many years ago. Steven Projan of Wyeth points out that compared to mammalian enzymes, bacterial enzymes are streamlined, with fewer of the nooks and crannies that are points of vulnerability for drug attack. We sometimes mistakenly think of bacteria as primitive, but they are more like state-of-the-art race cars: highly evolved and stripped down for performance. And clinical trials for an intravenous antibiotics are extremely costly. So the costs are higher and the profit potential is lower, which means that even if the researchers in Big Pharma want to do it, they have a hard time getting the project past their accounting departments.

I asked Steve Projan whether that meant that antibiotic development was something that should be done by the government rather than by private industry. His response was, "That might be one way to go, but I don't think it would be politically feasible--imagine the political fallout if they spent a billion dollars only to have the drug wash out in late stages of clinical testing? That's something that happens all the time in drug discovery."

I used to work for a Big Pharma company. I loved it. My work contributed to saving lives (maybe it still does). Now i work for a car company. Cars kill more people than i could have ever saved. So, in theory, i could save more people here than there.

The difference between theory and practice is that, in theory, they are the same.