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ROCHESTER — At the online premiere on Tuesday of "Finding Substance X," Mayo Clinic Heritage Films' new industrial reel on the discovery of cortisone, the celebrated story of the Clinic's finest hour opened with a familiar sequence of events.

There was the Ken Burns-like photography of an overflow crowd for an April 21, 1949 lecture by Drs. Edward Kendall and Philip Hench. Word had leaked that the pair would announce the effects of cortisone on patients with rheumatoid arthritis, news that would quickly travel the globe.

There was the archival footage of patients restored by the mystery drug, a Mayo-discovered, Merck-synthesized version of the body's anti-inflammatory hormone and an innovation that remains, in the view of many, second only to penicillin in the pantheon of medical discoveries.

The new film shares a now-famous story of the first cortisone trial subject. Upon receiving mega injections of the experimental substance, Mrs. G., a bedridden patient from Indiana, went from being unable to roll over to climbing the hill behind Saint Marys.

Following a week on cortisone, she set out on a three-hour shopping trip in downtown Rochester — in late April weather, before the subways — with the narrator adding how "she assured the doctors, I never felt better in my life."

"Finding Substance X" efficiently explores the long, halting backstory of cortisone — its genesis in an 18-year journey only made possible by determination, teamwork and a wartime effort to beat the Nazis in a race for serum to sustain pilots at high altitude.

The new film notes the humanitarian agreement to relinquish the patent, a trip to Stockholm for the Nobel Prize and how the pair shared their new funds so that a Franciscan sister who ran the arthritis floor could travel to Rome for an audience with the pope.

Most of these details are charming and well-reported. In the capable hands of writer and director Tom Williams, "Finding Substance X" could easily fit right in with the very best of public television.

But a notable deepening to the cortisone story finally emerges at the 18-minute mark, all thanks to a snippet of audio from that electrifying announcement in 1949.

As Kendall noted how patients quickly had lost their gains upon discontinuance of the new drug, he added a caution that researchers still needed to "learn how effective these compounds may be over a prolonged period, and how safe they are" over time as well.

In producing "Finding Substance X," the Clinic has seemingly incorporated elements from the book, " The Quest for Cortisone ," Dr. Thom Rooke's engaging and wide-ranging history of the discovery.

It is a title which describes both the highs as well as the lows of the story and its place in not just medical, but American political history. The latter includes the way in which the life of John F. Kennedy came to represent all the vexing potential and peril of the new drug.

As a young man, as Rooke and others have noted, nascent forms of steroids were given to the future president for intestinal troubles, drugs that may have caused Kennedy's adrenal glands to cease producing cortisone, and a treatment cascade that may have caused the bones of his spine to collapse.

Some even believe, had he not been confined to a back brace, Kennedy might have ducked following the first, non-fatal shot on Nov. 22, 1963.

As we know today, cortisone and the numerous steroid medications it spawned provide symptom relief for conditions where the immune system is the agent of harm. Cortisone mimics the "fight" of our fight-or-flight response, constricting blood vessels, suppressing immune function, imparting vigor and buying powers that are by definition only temporary.

This has offered countless gifts for the easing of suffering. Today, cortisone keeps Addison's patients alive — my wife is one — and it has saved millions from early death due to a long list of illnesses that include COVID-19.

Yet cortisone operates only in a small window of function, beyond which it can destroy the body in any number of ways.

The new film does not go into it, but as Rooke's book notes, Mrs. G subsequently developed moon face and psychosis following just a month on her megadoses of cortisone. When they released her from the psychiatry ward, she preferred arthritis to taking the drug, and died just 10 years later from bleeding that panelists on Tuesday suggested was likely due to the drug.

She wasn't the only one. Known to create grandiosity and mood swings, by the mid-1950s, cortisone had triggered so much madness they even made a movie about it, "an Eisenhower-era throat-grabber" called "Bigger than Life," starring James Mason.

These reports left Hench a changed man. By his later years, friends described him as depressed and irritable.

He could not have seen that his discovery was wholly perfect in its imperfect lesson that we cannot expect a bodily substance to do more than create balance where there is imbalance.

It is a truism first noted by a Swiss physician named Paracelsus, almost 500 years ago, and it applies to far more than cortisone.

He said it in reference to all things, and it seems like pessimism though it is nothing of the kind, and it has also been restated as follows: All drugs are poison, and the dose makes the poison.