Science on fast-forward

As an undergraduate, I was captured by the attitudes of humanity majors vs. those of us in science and engineering. We were in labs all afternoon and they were in the library napping or playing bridge at my literary fraternity. Many of my “brothers” were from prep schools and had a great facility with the written language, turning out papers in history and philosophy as they would later prepare legal briefs at hourly rates unknown to but a few in science. We would debate. It became clear that science was too immersed in impersonal data to be an acceptable humanity. I disagreed then and disagree even more today.

Science is a liberal art and subject to all the debate, uncertainty and interpretations as the origins of the great wars or the meaning of a Vincent van Gogh painting. On most topics, science advances very slowly and does not come to public light. Many don’t realize how little “settled science” we’ve got. What we think we know is subject to the next series of experiments. Scientists and engineers are typically introverts moving cautiously, learning in the background from our many mistakes.

The last nine months have brought science out front on a new scale. With nearly eight billion of us under a pandemic threat, our focus is uniquely sharpened. What’s going on? What should I do? Whose fault is this? Who can I trust? When will it end? Am I infected? How can we treat it? Follow the science. “Listen to the experts,” say the nonexperts.

Don’t panic. The “novel” adjective is the key and early on should have suggested attention to Rumsfeld’s notion of unknown unknowns, known unknowns and known knowns. The exact quote from the Secretary of Defense in 2002 went like this: ”There are known knowns. There are things we know that we know. There are known unknowns. That is to say, there are things that we now know we don’t know. But there are also unknown unknowns. There are things we do not know we don’t know.”

The same wordsmith also reminded us that, ”You go to war with the army you have, not the army you might want or wish to have at a later time.”

While he was widely ridiculed, I admired the twinkle in Rumsfeld’s eyes when asked probing questions at press conferences. These two observations seem to fit the current occasion especially well. We have a lot of creative reimagining going on now as we watch science and medicine advance as liberal arts.

Physicians had to try things early based on best guesses from known practice. “Let’s try this and see what happens” is very much a part of innovation in all areas. The ICU patients can’t wait for controlled trials. In critical care, double-blind placebo-controlled trials are senseless. Fortunately, we have off-label uses for known therapeutics. We can only guess at an appropriate dose for the novel use. Early, it was hard to segregate patients based on risk. Within a few months, that began to clarify. It was certainly appropriate to panic over ventilator capacity and quickly remedy it. That was smart.

We overshot as the known unknowns began to clarify. The same was the case for expanding ICU capacity. That we can do that and know how to do it takes another unknown known into the known known category. “Yes, we can.” But let’s not forget to be more prepared next time.

Global market size in an emergency sharpens the science and business motivations. Activities that typically take five years of careful planning and fundraising were brought into action in weeks. Hundreds of firms jumped on diagnostic test development for emergency use. Old drugs and new were explored for the virus and its downstream consequences. Discovery to preclinical animal work to early-phase trials happened in months.

We already have multiple vaccines in Phase 3 trials in less than 12 months. Wow! Early tests were very poor. Many were withdrawn. New and old drugs worked in some of the patients some of the time at some of the doses. This is perfectly normal. Political science has kicked in too, with unsatisfying results. Expressing hope for this or that is fine; predicting outcomes on a schedule is foolish when so much is unknown.

We have a great opportunity to better educate the public on the complex web of promised financial and political returns. The triumph of data over hope.

Known science is just beginning to beat “trying things.” Much good has been accomplished. Quoting Winston Churchill from November 1942, following a major defeat of Rommel’s army in Egypt, “Now this is not the end. It is not even the beginning of the end, but it is, perhaps, the end of the beginning.” This war will not end soon, but we’ve learned a lot.

Readers of DDN: Keep going. You are doing great work. Get good data and keep your investor relations people under control. Collaboration among pharma has been unprecedented. Auto companies manufacturing ventilators reminds me of Ford building B-25s in the 1940s. Thanks also to the millions of patients who unknowingly participated in impromptu clinical trials, and condolences to those who died in this COVID-19 war. Their lives have not been given in vain. We will long remember them.

Peter T. Kissinger (who can be reached at kissinger@ddn-news.com) is a professor emeritus at Purdue University, founder of BASi, chairman of Phlebotics and director of both Prosolia and Tymora.