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Resistance Is Futile: Why That’s A Good Thing In Biomedicine

Opinion

Xconomy Seattle — 

Fans of Star Trek: The Next Generation are very familiar with the Borg, a society of cybernetic individuals linked together in a collective mindset. The Borg navigate the universe in cube-shaped spacecraft actively seeking members of other races to absorb into their collective. Whenever others oppose their efforts, the Borg let them know, in no uncertain terms, that “resistance is futile” and they will be assimilated. Without context, however, this phrase can be interpreted in several ways: are we talking about resistance to change, or resistance to orthodoxy?

I was thinking about this catchphrase when I was reading Christin O’Keefe Aptowicz’s historical biography, Dr. Mütter’s Marvels: A True Tale of Intrigue and Innovation at the Dawn of Modern Medicine. The book details the career of Dr. Thomas Mütter, a pioneering surgeon working in Philadelphia in the decades just before the U.S. Civil War. It describes the state of doctoring in America during that time period, and recounts how Dr. Mütter and some of his colleagues tried to introduce several new advances in medicine. These included (1) the use of ether anesthesia in surgery, and (2) the concept that operations should be done under as clean a condition as possible to prevent disease in both the primary as well as subsequent patients.

What was surprising was how efforts to introduce these changes were met with tremendous opposition from many members of the medical establishment. This resistance, of course, thankfully proved to be futile in the long run. As additional data were accumulated with more clinical experience, it became clear that these changes to the existing orthodoxy would both prevent patient suffering and significantly decrease mortality. It is an early example of empirical research and outcomes-based experimentation on people. As industrial designer and futurist Buckminster Fuller later put it, “You never change things by fighting the existing reality. To change something, build a new model that makes the existing model obsolete.”

Can you imagine undergoing surgery without the benefit of anesthetics? Can you picture your surgeon operating on you without washing his hands and while wearing a filthy surgical gown? The book is filled with horrifying descriptions of many of the medical procedures used in that era, and it reads like the fusion of a Stephen King novel with a touch of the Saw movies thrown in. During this time period, the best surgeons were renowned for their speed and the ambidextrous skills with which they handled the knife. Amputations, mending mangled limbs, repairing birth defects (such as cleft palates and club feet), and fixing the terrible scarring that resulted from fires were all procedures that were routinely done in the mid 1800s. A team of strong men was often part of the medical team, their job being to physically restrain the patient during the operation. These days, of course, the deliberate infliction of extremely painful medical procedures would be viewed as torture by most civilized people (with the possible exception of Dick Cheney).

Who Would Be Opposed to Anesthesia? And Why?

So why were many doctors strongly opposed to the introduction of inhalation anesthesia? There were essentially two reasons. The first was that the quality of the new ether-based anesthetics was, to put it charitably, not very good. Manufacturing of these agents had not been standardized, and there was significant batch-to-batch variability in purity and strength, which on occasion led to patients dying from too much anesthesia. Dosages were being worked out on an empirical basis. Edward Robinson Squibb, a Navy physician, took on the task of producing a pure and reliable source of ether, though he famously declined to patent either the process or the design of his apparatus. He went on to establish the pharmaceutical company bearing his name, which is now part of Bristol-Myers Squibb.

The second reason for opposing anesthesia was more of a philosophical and religious one. The conditions that physicians were called upon to correct, such as congenital deformities or injuries, were viewed by some as God’s will. The pain that patients had to endure in surgery was seen as part of God’s punishment for whatever transgressions had landed them on the operating table. Freeing patients from such agonies was viewed in some quarters as opposing God’s plan.

It was easier to understand why there was opposition to keeping the surgical suite as clean as possible, since this was before the discovery that infectious diseases were caused by microorganisms. The first antibiotics were still more than fifty years from being discovered, and Louis Pasteur, Joseph Lister, and others had not yet been developed the germ theory of disease. Ideas about what caused certain diseases to spread were still being actively debated, and the concept of epidemiology was just being birthed. The prevailing view at the time was that a noxious form of “bad air” caused diseases. A British physician, John Snow, is credited with stopping a cholera epidemic in London in 1854 by getting local authorities to remove the handle on the Broad Street water pump that he identified as the source of the outbreak. Ignaz Semmelweis, a Hungarian obstetrician, figured out around this same time that doctors were spreading the often-fatal puerperal fever among women in the Vienna General Hospital’s maternity ward. He ordered them to wash their hands using a chlorinated lime solution, and this reduced the mortality rate of childbirth by 90 percent. You might think that Semmelweis would have achieved a level of respect and admiration from his colleagues with this discovery. In fact, he was ridiculed and scorned by his fellow doctors, most of who considered themselves “gentlemen” and therefore were above being “unclean” and spreading disease.

What is the Basis for Resistance to New Ideas?

Generally speaking, there are five elements that contribute to this resistance:

1) No data. Ideas are often rejected out of hand if there are simply no data to support them, even if the concept matches up well with current observations. In these cases, opponents can sometimes be easily converted once empirical data are obtained in support of the new idea.

2) Idea is contradicted by “what everybody knows is true.” In this situation, opponents are not even interested in looking at new data, because the new idea is simply not worth considering. As George Bernard Shaw put it, “Beware of false knowledge; it is more dangerous than ignorance.”

3) In order for new solutions to be looked at critically, opponents must accept that the problem actually exists. For example, it will be difficult to come up with solutions to the problems of global warming as long as certain politicians refuse to accept the fact that the earth is getting warmer.

4) Religious conviction. Ideas that don’t match up with “scripture” are often rejected out of hand, no matter how much data are available to support them. This type of thinking and its ramifications were nicely illustrated in Edward Humes’ 2008 book, Monkey Girl: Evolution, Education, Religion, and the Battle for America’s Soul. The book details efforts to teach “intelligent design” in addition to evolution in public schools.

5) Acceptance of the idea eliminates financial rewards. Many ideas are opposed because they will cut into peoples’ income, giving them a strong financial disincentive to change their thinking. Otis Brawley, chief medical officer of the American Cancer Society, summed this up nicely when he said, “We in medicine need to look into our soul and we need to learn the truth. If your income is dependent on you not understanding something, it is very easy not to understand something.”

New Ideas in Biomedicine Still Take Time to be Accepted

Resistance to change of the status quo has been a facet of biomedicine (and many other fields as well) for hundreds, if not thousands, of years. One does not have to go back to the era of Mütter and Semmelweis to find opposition to new ideas within biomedicine. It can still be found in surgical suites, as documented by Dr. Atul Gawande’s book, The Checklist Manifesto. He details how significant resistance was met when efforts were first made to introduce checklists into operating room protocols. Resistance in biomedicine is not limited to surgeons. Two other examples that come to mind:

—The idea that bacteria, not stress, were the cause of gastritis and gastric ulcers was widely ridiculed not that long ago because doctors could not believe that bacteria could survive in the acidic environment in the stomach. Barry Marshall, an Australian physician, challenged this thinking by doing an experiment and deliberately infecting himself with the suspected bacterial strain and then curing himself with antibiotics. Subsequent clinical trials replicated this finding and led to Dr. Marshall and his colleague Robin Warren winning the Nobel Prize in 2005.

—The central dogma in biology teaches that DNA is transcribed into RNA, which is then used to direct the production of proteins in the cell. Back in 1970, virologist Howard Temin proposed that RNA tumor viruses contained an enzyme that could do the opposite: transcribe RNA into DNA. This hypothetical enzyme was given the name reverse transcriptase, and its existence was widely doubted. Experiments done by Temin and independently by David Baltimore showed that such an enzyme truly existed, and they shared the 1975 Nobel Prize for this work (along with Renato Dulbecco).

Still working their way through the resistance paradigm in health and biomedicine are a number of new ideas, including the concept of precision medicine that is tailored to each patient, the possibility that e-cigarettes may be harmful to one’s well-being, and the potential health benefits of golden rice in third world countries.

Resistance to Change is Not Limited to Biomedicine

Looking back at U.S. history, it is easy to highlight numerous practices that survived because people were resistant to change. Among them: slavery, racial injustice, anti-Semitism, eugenics, opposition to gay marriage, laws opposing miscegenation and the rights of women to vote, own property, and have credit in their own names. These and a host of other discriminatory issues were once commonplace in society, but eventually they gave way to the forces of change. Sometimes change happens rapidly, but other times it’s a process that slowly slogs its way through the shifting sands of time. Perseverance is required of those who seek change, and there will often be setbacks as one travels what can often be a lonely road. Trust that if you are on the right path, resistance to your cause will, in the long run, be futile. Andy Warhol was right when he said, “They always say time changes things, but you actually have to change them yourself.”

Stewart Lyman is Owner and Manager of Lyman BioPharma Consulting LLC in Seattle. He provides strategic advice to clients on their research programs, collaboration management issues, as well as preclinical data reviews. Follow @

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