Ask a ScienceBlogger: What era of science?

You may have noticed that I opted out of the last two or three weeks worth of Ask a ScienceBlogger questions. The last couple of weeks it was because the questions simply didn't interest me, and the week before that it was because i just plain forgot.

This week, however, our overlords at SEED Magazine demand:

If you could have practiced science in any time and any place throughout history, which would it be, and why?

That's a pretty easy one. I'm with Stein in that I answer: Now.

Think about it. I'm a physician, and my interest is in studying cancer. I started graduate school in 1990. Since then, in a mere 16 years, the tools that have become available to study human physiology, genetics, and disease are astounding. We have sequenced the human genome and are now busily analyzing the data. For the first time ever, we can now measure the expression of every gene cells or tissues on a single chip, analyze the results, and identify signaling pathways that change based on changes in clusters of genes in response to stimuli or drugs. This new science (known as genomics or genomic medicine) is something that was unimaginable a mere 15 years ago. Now, because RNA expression doesn't always correlate with expression of the functional protein, we are now moving towards proteomics, where we measure the proteins expressed by cells.

It's all simply amazing to me. I have tools I never would have dreamed of even in graduate school, and these tools have come into existence in an incredibly short period of time. What new tools will be developed in the next fifteen years?

In terms of treating cancer patients, the advances have come almost as fast. Alties will condemn conventional oncologists for "poisoning," "burning," and "cutting" tissue. (As a surgeon, I guess I represent the "cutting" part.) However, less appreciated is that the major focus of cancer research has shifted to looking for less toxic therapies that do the job as well with far fewer side effects as the old chemotherapeutic regimens of the past, with the targeting of tumor angiogenesis (one of my areas of interest) being one such promising strategy. The same is true in surgery. Take breast cancer, for instance. In just the time since I graduated from medical school, we have gone from a high percentage of women getting mastectomies to being able to save the breast in 2/3 to 3/4 of women. We have gone from removing nearly all the lymph nodes under the arm on the side of the breast cancer, with all the attendant complications of lymphedema, arm pain and numbness, and decreased range of motion, to sampling only one to three lymph nodes and getting the staging information we need, reserving complete lymph node dissections only for women who have positive lymph nodes. We are tailoring our therapy to molecular targets, for example the Her-2/neu oncogene, with the promise of more targeted therapies to come.

What other time period could offer so much promise?

More like this

I remember reading an article where Eric Lander made the statement (paraphrasing): 'Can you imagine what people 15-20 years from now will think about the current way we do medicine? They might say: Can you imagine, they use to poison people back then to try to treat cancer.. Won't that be great'
He's referring exactly to what you are referring to as well, that advancement in medicine and technology where we might be able to target the cancer cells more specifically instead of our scatter-shot approach.

Funny thought that just occured to me: Dr. McCoy of Star Trek winds up in current day Earth with a 29th or so century time traveler. McCoy compares surgery to bleeding and primitive amputations. 29th Century guy: "You're one to talk! You use hyposprays and tricorders!"

I'd also add that "we" have learned a helluva lot more about how to use chemotherapy, these so-called poisons, to give them a greater therapeutic index or window of safety. Regular folks are often surprised sometimes to learn that all of these newer "targeted therapies" still need small molecule, conventional cytotoxic agents to work (Avastin, for example).

What really blows me away are things that we are still learning about old drug today: for example, the idea that low-dose continuous chemotherapy, or metronomic chemotherapy, may provide a great margin of safety by acting in an antiangiogenic fashion rather than as frank cytotoxins (there was a superb review in one of the Nature journals by Orac's idol, Judah Folkman, and Sunnybrook/Toronto's Bob Kerbel that speaks to this notion).

So, I kind of disagree with Lander. I've spent the last 21 years since starting grad school listening to molecular biologist tell me how they are going to cure cancer and how we small molecule folks are just concocting new poisons. But then they learn about basic concepts of pharmaceutics and the difficulties in delivering peptides or nuclei acid therapeutics, the fact the test tubes and Petri dishes don't have a liver or kidneys, and other physicochemical issues that folks now refer to as Lipinski's rules of five.

So, I think we're doing pretty good now but have to be vigilant against the hype of "the next big thing." Taking what we already have (cytotoxic chemotherapy) and using it more wisely and, perhaps, in conjunction with pharmacogenomic analysis and giving drugs to those patients whose tumors are most likely to respond will, I predict, continue to pay greater dividends than the overhyped fields of siRNA or gene therapy.

For the biological sciences 'now' would be a very good choice -- well, almost. I think it will take about another six years for the effects of the Bush Administration's War on Science to fade. This can't make 'doing science' more pleasurable.

But I'll have to admit that, were I a physicist, the thought of living in the 'time between the wars' and being around the work being done then and the particularly wonderful group of characters doing it would be a dream. Bohr, Einstein, Fermi, Gamow, Oppenheimer, etc. Wow! (And, given the danger of Hitler, I would not have had objections to working on the Manhattan Project, though the post-war events would have done much to kill the feeling of accomplishment.)