OBJECTIVE SCIENCE: AN INHERENT OXYMORON

LAURANCE JOHNSTON, PH.D.

There are more things in heaven and earth than in most scientists’ philosophy. – William Shakespeare, Hamlet.

At a recent conference on spinal cord injury (SCI), a scientist expressed concern that I was writing about therapies that have not been proven by the rigorous standards of objective science as defined by him and like-minded colleagues. As someone who has been involved in the scientific process for decades, including at high policymaking levels, I thought his science-is-a-sacred-cow attitude was pretty naive.

Although an invaluable sign post guiding us to new knowledge, the scientific process is imbued at all levels – from the economic to the most basic observation - with subjectivity. The more we ignore this fundamental truth and maintain an unswerving allegiance to a putatively objective, but in reality systemically subjective, scientific process, the less effective we ultimately will be in developing real-world therapies for many disorders.

This article will discuss several diverse examples of subjectivity in the scientific world.

Double Blind or Double Standard

In his advocacy of high scientific standards, the aforementioned scientist apparently was unaware that most routinely practiced medical practices do not meet such standards. Specifically, the Congressional Office of Technology Assessment (as well as others) concluded that only about 10-20% of such practices have been scientifically proven. Most of them have been grandfathered in based on experience, in other words, getting a “free pass” scientifically. In contrast, new innovative, much needed therapies face huge regulatory hurdles to meet ever-increasing scientific standards. In the case of disorders such as SCI, which have a relatively limited economic market, strict adherence to these standards will ensure a snail-pace development of new therapies.

This double-standard hypocrisy is systemic in biomedicine. For example, at the same conference mentioned above, a U.S. scientist was highly critical of an innovative (albeit, indeed, questionable), function-restoring therapy being developed in China, primarily because it had been made available to the public without sufficient rigorous testing. Defending the innovator, one of the field’s foremost scientists later noted that this critic routinely performs surgical procedures that lack the testing he is demanding from the Chinese innovator – i.e., not practicing what he preaches.

Lessons of History

If we learn anything from the lessons of history - such as the persecution of Galileo for proving that the Earth moves around the sun or the ridicule of Ignaz Semmelweis for audaciously suggesting that physicians wash their hands - it is that today’s state-of-the-art, often righteously held scientific beliefs will be tomorrow’s anachronisms. The only factor that distinguishes present scientific truths from those of the past is subjective judgments based on the summation of many also subjective, scientific assessments and observations.  

Early in my scientific career, I had the good fortune to meet several of the modern age’s titans of science, whose breakthrough discoveries show how non-objective science can be in some capacity.  For example, as a fledging biochemist, I met Sir Hans Krebs, who was awarded the 1953 Nobel Prize for elucidating metabolic pathways that are now at the foundation of medicine. He showed a slide of a letter he had received from the prestigious journal Nature rejecting his seminal work for publication due to insufficient scientific merit, as it turns out, a totally wrong subjective evaluation by the journal’s scientific advisors.

Today, as I write about therapies that frequently challenge today’s status-quo, I often reflect on Krebs’ rejection letter. If the father of modern biomedicine could be rejected by prestigious scientific authorities, I wonder what innovative, humanity-helping therapies our experts are rejecting today based on their subjective, limited views of the world.

About the same time, I also met Dr. Francis Crick, who was awarded the Nobel Prize (1962) for elucidating the structure of DNA, the molecule at the core of life. Later in his life, he acknowledged that he perceived the double-helix structure of DNA under the influence of LSD. It is “mind-blowing” to think that it took a drug-induced altered state of consciousness, different way of looking at the world, or shift in imprisoning paradigms to come up with one of mankind’s most profound discoveries.

Intuitive vs. Objective Science

Science is not supposed to work this way; it has well-defined procedural rules. Nevertheless, such expanded or intuitive insights, however they may be triggered (dreams, meditations, it-came-out-of-the-blue epiphanies, etc), play a much larger role than is acknowledged for many breakthroughs.

One of history’s more well-known examples is the discovery by Dr. August Kekule, a famous 19^th century German organic chemist, of the structure of benzene. His breakthrough came in a hypnagogic state after he dozed off in an easy chair in front of his fireplace. Because of potential ridicule from colleagues, most scientists are reluctant to admit that their breakthroughs may have been inspired through such non-traditional insights.

This observation does not suggest that science should lack rigor, reflecting Louis Pasteur’s statement “In the fields of observation, chance favors only the prepared mind.” Like the yin-yang symbol of wholeness, the best scientists have learned how to integrate the intuitive with the objective. For example, Crick was an exceedingly well-trained scientist, whose altered-consciousness insights, just synergistically complemented his disciplined scientific observations.

In a rough analogy, the difference between playing by the scientific rules and a more expansive, creative process is like the computer playing chess against the strategically insightful grandmaster. The computer-like scientist has to go through a lot of experimental iterations to make progress and lacks the computer’s speed for effectively doing so. Unencumbered with the blinders of the scientific process, the “grandmaster” scientist has a more expanded vision of what is possible, can bypass procedural steps viewed as unnecessary, and, in turn, can make the quantum-leap forward.

Native American philosophy reveals useful insights. Specifically, in The Way of the Scout (1995), author Tom Brown, Jr. describes how when he was a child an Apache elder taught him to use an “expanded focus,” where the task or objective is but a small part of the whole picture. When we relax an absolute focus (i.e., the scientific process), we become more aware of life’s flow around us, and, as a result, assistance or insights in many unanticipated forms becomes available.

The scientists who restrict themselves to the sanctioned formula are essentially no more than super technicians. In contrast are the scientists who subordinate the scientific process to their creative, expanded insights. They understand the process is an invaluable tool, but they are like artists who realize the great choice on their experimental palette to paint the big picture.

Subjectivity at the National Institutes of Health

With a $29-billion budget, NIH is the world’s most prestigious and powerful biomedical agency. Through an involved grant-application process, the agency funds most of the biomedical research carried out at nation’s hospitals, universities, and research institutions. When it comes to setting the nation’s biomedical agenda, NIH is the 800-pound gorilla. Although the agency’s public health contributions have been immense, its decision-making is influenced by host of factors and agendas other than strict objective science.

In 2006, NIH received ~46,000 grant applications requesting funds that greatly exceeded its budget, for example, at some Institutes funding only 10% of worthy applications. NIH prioritizes the applications by merit through committees of expert scientists, who review submissions and assign priority scores. Because of insufficient funds, most, even highly meritorious, applications cannot be funded. Although the peer-review process sounds good in theory, it was not designed to handle the volume of applications that NIH now receives.

I was in charge of this process at one of the NIH institutes, and, in that role, managed the peer review of thousands of applications. The priority setting can be greatly influenced by review-team composition and dynamics, including the very subjective scientific viewpoints and priorities of its members. For example, if I was going to review clinical trial applications, I could recruit a team composed of scientists emphasizing study-design (e.g., biostatisticians, epidemiologists, etc) or clinicians with a hands-on appreciation of the issues being studied. Each group would have very different beliefs on what issues were important, and the relative proposal ranking could vary greatly depending upon which disciplines predominated. Clearly, whose “objective science” prevailed was a subjective decision, which I, in part, controlled.

Based on such factors, it was easy to set up a highly critical or forgiving review team if so desired. If, for example, Congress had allocated a million dollars to fund a targeted research program in a specific fiscal year and time was of the essence. I’d guarantee that the recruited review team, albeit high qualified, would be more merciful in its critique.

At NIH, I organized review teams in many different scientific disciplines, and, in general, was constantly amazed how little appreciation one discipline had for the priorities of an even closely related discipline. Although solutions to today’s problems will require open-minded multidisciplinary thinking, it seemed that everyone’s field of vision was parochial in outlook.

The one discipline above this parochialism was supposedly statistics. Used to anoint study validity, the discipline is viewed as objective-science’s foundation stone that transcends all subjectivity. But does it? Perhaps Mark Twain’s statement is more indicative of its true nature: “There are three kinds of lies: lies, damned lies, and statistics.” Twain’s wisdom is reflected in a recent article by Dr. John P.A. Ioannidis, which discusses the flawed statistical assumptions inherent in many studies. He concludes “for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias.”

Subjectivity & Innovation:

Although many disorders desperately need innovative solutions, NIH’s prioritization process is generally not well suited to generate them. For example, if only 10% of proposals can be funded, applicants are going to play it safe, developing proposals that won’t be too challenging to the peer-review committee’s prevailing scientific paradigms.

NIH has always had problems funding innovative research. As a rough analogy, its peer-review process is like choosing a movie to rent as a consensus decision with your wife, family, and friends, all of whom have different priorities. To get everyone to concur in the choice will guarantee mediocrity, not inspiration.

The most exciting developments for many disorders are emerging in other parts of the world. Instead of paying attention to these developments as worthy of further exploration, NIH tends to ignore or dismiss them, convinced of the superiority of its approaches. Even if there were hundreds of promising anecdotal cases, which is, indeed, the situation for some innovations, they don’t matter from NIH’s viewpoint.

Although NIH-funded investigators are unsurpassed when it comes to basic science or delineating physiological mechanisms of action, because their hands are shackled by many constraints, they are falling behind in translating that knowledge into real-world therapies. They believe that they are sprinting for the gold medal not realizing that the runners next to them from other parts of the world have already lapped them. Yet, who does NIH rely on to set priorities but the runners being lapped, whose scientific careers rely more on allegiance to the status-quo than the priorities of the disability community.  

Finally, pioneering innovators throughout the world are frequently criticized because they haven’t published their work in peer-reviewed journals, but usually it is a frustrating, uphill struggle when they try. Though out my career, I’ve consistently seen some incredibly mediocre, so-what research published, while most quantum-leap-forward research that we need to know about is rejected. Clearly, mediocre endpoints that don’t push the envelope are more amenable to the scientific scrutiny required for publication than question-generating, innovative research. We need a publication mechanism by which the innovative, with all of its “warts,” can be better disseminated to other researchers who have the potential to provide further answers. As the power of the Internet further develops, professional journals are going to be left in the dust in this regard.

Disability Perspective:

When I managed NIH peer review, disability tended to be a theoretical issue, for example, a statistical power calculation justifying a sample size in a grant application. Generally, we only had token interactions with the disability community. As such, priorities were assigned primarily based on the evaluations of able-bodied scientists, who usually had little appreciation of the true priorities of individuals with disabilities.

Later, I became director of the Paralyzed Veterans of America’s Spinal Cord Research and Education Foundation. PVA had the heart and soul that was often lacking at NIH. Disability was personal; it was your colleagues, your bosses, and your friends. Although all grant applications were subjected to rigorous scientific review, funding decisions were made by scientists or doctors in wheelchairs. Subjective priorities often varied considerably between able-bodied scientists and those with disability.

Economics:

Considering economic factors such as the following, it is naïve to assume that the nation’s healthcare has been shaped by merely objective science:

• Physicians obtain most of their information on medicines from the profit-motivated, pharmaceutical industry.
• Most medical consultants that advise public-health agencies have financial conflicts of interest with the drug industry that their decisions profoundly influence.
• There is a strong association between author’s published positions on drug safety and their financial relationship with drug companies.
• Drug advertising has increased astronomically in recent years.
• Drug companies spend an average of $13,000/year on each U.S. physician to market their products. 

The Effect of Consciousness on Scientific Observation

All scientific observation - even at the most fundamental level - is affected by the observer’s consciousness. In this regard the statement “I’ll see it when I believe it,” is more apropos than its commonly stated converse. Numerous studies have shown that consciousness exerts a significant influence on many different endpoints, ranging from bacterial growth to the outcomes of heart patients.

Double-blind clinical trials, in which neither the subject nor the physician knows who is receiving the active agent, are considered the gold-standard in research methodology. Although developed to reduce both investigator bias and patient placebo effect, the expectations of the blinded investigators have been shown to influence study outcomes. For example, when there is much enthusiasm for the drug when, for instance, it is first introduced, the excitement percolates into the study, producing more robust effects. Over time, when other, more efficacious agents have been developed and investigator enthusiasm has waned for the original drug, the effects become less pronounced and can even disappear statistically.

Studies have actually been designed to measure this effect. Specifically, it has been demonstrated that the beneficial effects when an enthusiastic investigator (e.g., the drug discoverer) managed a double-blind study can fade into insignificance under the direction of a more detached skeptic.

The potential influence of consciousness on scientific observation is underscored by numerous quantum-physic theories, especially the famous Heisenberg uncertainty principle. Basically, this theory states that the more precisely the observer measures electron movement, the more uncertain he is of its position and vice versa. Although how much this truth determines our macro-reality has been extensively debated, it implies that the very act of observation, including the dynamics of the observation process, changes the object being observed. In other words, the observer and all of his subjective baggage is a part of the experiment.

Commenting on the behavior of photons, noted quantum physicist Dr. John Wheeler stated “No phenomenon is a phenomenon until it is an observed phenomenon “The universe does not ‘exist, out there.’ . . . It is in some strange sense a participatory universe.”

In his book The Universe in a Single Atom: The Convergence of Science and Spirituality, the Dalai Lama relates many quantum-physic theories, including Heisenberg’s uncertainty principle, to Buddhist philosophy. For example, under the key Buddhist theory of emptiness: “belief in an objective reality grounded in the assumption of intrinsic, independent existence is untenable. All things and events … are devoid of objective, independent existence.” Later, he notes that “anything that exists…does so only within the total network of everything that has a possible or potential relationship to it.” This philosophy suggests that the scientific observer and the observed are always connected and influence each other’s perceived reality.

Conclusion:

In conclusion, there is no such thing as objective science; it is affected at all levels with varying degrees of subjectivity. Indeed, quantum physics suggest that such subjectivity can never be truly eliminated. Like grasping one part of a balloon, the process of progressively, more intensely focusing on one factor will inherently change the characteristics of another aspect. In spite of undeniable contributions, objective science is only one of numerous equally valid ways of looking at the universe. For many scientists, however, it has become equivalent to a religion in which a system of beliefs is dogmatically embraced with passion and devotion. Convinced of its superiority, the faithful eschew the truths obtained by others who do not practice the sanctified liturgy. If we are going to develop big-picture solutions to problems that plague us, we need the contributions of different, but synergistic, ways of looking at the universe.  

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