As reported by NBC News, in 2016, a group led by Dr Peter Hotez, co-director of the Center for Vaccine Development at Texas Children’s Hospital and dean of the National School of Tropical Medicine at the Baylor College of Medicine in Houston, developed a vaccine for SARS (severe acute respiratory syndrome), an earlier coronavirus than the one behind today’s pandemic. But Dr Hotez was unable to get funding to test the vaccine on humans.
Hotez believes that his vaccine would work for the new coronavirus that causes Covid-19. He argues that had his team been able to test and further develop the vaccine, it would have been ready for testing when the new coronavirus first appeared.
He has testified before the US House of Representatives Committee on Science, Space and Technology, arguing that there needs to be reform of how research funding is awarded. He stated: “It’s tragic that we won’t have a vaccine ready for this epidemic…. Practically speaking, we’ll be fighting these outbreaks with one hand tied behind our backs.”
Professor Jason Schwartz of the Yale School of Public Health testified that medical research tends to be reactive rather than proactive. He said, “We have a pattern in our medical research landscape in which outbreaks lead to a surge in research investment, and if and when those outbreaks wane, as they invariably do, other priorities take their place…. As a result, you lose those opportunities to capitalize on that initial investment, and the cycle starts over again.”
Schwartz argued that governments and non-profits must take responsibility for long-term research because private pharmaceutical companies cannot be expected to fund projects that are likely never to make a profit.
This is an old argument that was once accepted as the very lifeblood of big engineering research, from development of the atomic bomb at Los Alamos, New Mexico, through the period of the space shuttles. Yet even the commitment made for those projects is insufficient for medicine, where the science remains rudimentary relative to the requirements of the applications.
Medicine is far superior to what it was 60 years ago. Much of this progress is due to improved technology, particularly imaging, with robotics coming on fast. If a physician knows what to do, he has outstanding tools to accomplish the task. The issue is whether he knows what to do. For that, he depends on biological knowledge, not the technological knowledge that has given him MRI (magnetic resonance imaging) and robotic surgery.
In the early 2000s, there was much talk of “translational science [medicine]” (see an excellent article in the Encyclopedia Britannica). Rather than biology and medicine going their own separate ways, with medical researchers making use of whatever scientific knowledge happens to be available, the needs of medicine would drive scientific discovery and the resulting scientific knowledge would be translated into medical application. While the terminology was descriptive, one could have simply called it “modern engineering.” Engineering translates scientific knowledge into actions that alter the physical world, and there are often strong connections between scientists and engineers.
Given the extreme complexity of biological systems, targeted basic research would be especially beneficial, because only by reducing a complex system can one hope to gain functional knowledge, and for a reduction to prove beneficial, it must be done in a way to preserve the information necessary to achieve the desired objective. This is a classical engineering paradigm.
The translational modeling of biological systems requires tight collaboration among scientists, engineers and physicians. This demands outstanding research directors to select critical problems, such as viruses and cancer, and to provide knowledgeable scientific leadership. It also requires teams of top-quality researchers who will learn sufficient amounts from the various disciplines involved so that there is productive communication. All of this necessitates stable funding (at least 10 years).
No one has understood the interdisciplinary problem better than Norbert Wiener, the father of modern engineering. His opinion on needed expertise deserves a long quotation from 1948:
“It is these boundary regions of science which offer the richest opportunities to the qualified investigator. They are at the same time the most refractory to the accepted techniques of mass attack and the division of labor. If the difficulty of a physiological problem is mathematical in essence, ten physiologists ignorant of mathematics will get precisely as far as one physiologist ignorant of mathematics. If a physiologist who knows no mathematics works together with a mathematician who knows no physiology, the one will be unable to state his problem in terms that the other can manipulate, and the second will be unable to put the answers in any form that the first can understand.…
“The mathematician need not have the skill to conduct a physiological experiment, but he must have the skill to understand one, to criticize one, and to suggest one. The physiologist need not be able to prove a certain mathematical theorem, but he must be able to grasp its physiological significance and tell the mathematician for what he should look.”
Government funding does not encourage this kind of collaboration. People need to be brought together and given the time and resources to develop collaborative expertise. Instead, there are multi-institution grants of short duration where researchers across different disciplines and institutions are supposed to collaborate. The result is some commonality of research, but people tend to go their own ways, recognizing that the entire operation will be short-lived, and their careers are dependent upon their contributions in their own fields.
When it comes to medicine, what kind of interdisciplinary approach should we expect? It is not just engineering in general that is important, but the right engineering for the problem. Here again we should turn to Norbert Wiener, who in 1948 noted the “essential unity of the set of problems centering about communication, control, and statistical mechanics, whether in the machine or in living tissue.”
No more important words for medical research have ever been written.
Given what is known today about both intra- and inter-cellular communication, Wiener’s point is obvious. Chemical signals are processed by the cell and signals are used in conjunction with logic-like regulatory mechanisms. Engineers know this kind of problem well, and for 75 years have been utilizing control theory in conjunction with signal processing to regulate systems. If cell regulation becomes aberrant, external control (for instance, drugs) can be used to control regulation in an optimal manner.
Wiener’s analysis of the fundamental medical problem runs right into his recognition of the kind of research structure needed to address it. You will find very few specialists in statistical signal processing or control theory at the US National Cancer Institute, nor will you find them in environments where there is sustainable collaboration and funding for medical research. Wiener has been ignored.
Will the current pandemic make political leaders listen to the greatest engineering mind in history? Their draconian actions demonstrate that they recognize the gravity of the situation. One might therefore hope that, once the crisis passes, they will make the necessary changes. But our leaders are politicians. They will depend on their scientific, engineering and medical advisers to implement the kind of changes implicit in Wiener’s thinking. Are these up to the task?
The best young mathematical minds need to be recruited into biomedical research. This means establishing the required educational infrastructure at top universities. Biology departments should mathematically resemble physics departments, the difference being that physical laws are replaced by biological laws. Such a dramatic re-restructuring demands strong impetus, more so than under US president Dwight Eisenhower in the 1950s, when there was the palpable threat of nuclear war with the Soviet Union.
In those days the task was to build a research structure. Today, it is to revamp a massive administrative structure. Institutions have to be reorganized and new leadership put into place. Power and money have to be moved into different hands. People who now hold power must relinquish power to those with suitable ability and training to lead the Wiener transformation. History holds out little hope for such reasonable behavior, but it does have many instances of strong leaders, including Eisenhower, forcing necessary changes.
Let me close with a quote from a paper on the limitations of biological knowledge that I wrote eight years ago with a brilliant young colleague of mine (whom I would presume to say would be an excellent person for the current US president to call upon to help implement the Wiener approach to medicine):
“The issue here is one of purpose. Do we as a community sufficiently desire knowledge to address the difficult problems standing in the way of knowledge? There can be no doubt that human beings possess the intellectual capacity to solve many of the problems because, as a species, we have solved harder problems, so this is not an issue of human capacity; rather, it is an issue of human choice.”
(From Dougherty, E R, and I Shmulevich, “On the Limitations of Biological Knowledge,” Current Genomics, Vol 13, No 7, 574-587, 2012.)