Revisiting the approach to Y2K, looking out to Y2K+20

Time gets away from me, or let’s say it is accelerating away. I recently asked university students if they were familiar with the term Y2K. They’d generally not heard of it, although one said, “I was a Y2K baby and will soon be 19.” That’s a sobering thought. Most DDNews readers today were conscious beings long before that recent past.

Twenty years ago, there was much anticipation for Dec. 31,1999. Some looked toward an excuse for a super New Year’s party, while the party poopers generated anxiety over a growing dependence on information technology (IT). When we rolled into Jan. 1, 2000, prognosticators assured us we’d be infected with the “millennium bug.” This would, they said, disable power generation, corrupt commuter networks and generally cause havoc with a year described by four digits instead of two. [Editor’s note: For those too young to have fully appreciated the year 2000, the millennium bug was not malware but a problem with the fact many computer systems used the last two digits of the calendar year only, instead of all four digits, leading to potential system confusion between the years 1900 and 2000.]

At the time, as a supplier of products and services to pharma, our company was asked by procurement officers to certify that our products had no such bugs and to accept full liability if they did. The anxiety was so far-reaching that we were to certify for items that had no IT component at all. Time and money were spent. In the end, the clock changed, and nothing happened. Twenty years later, we again suffer from IT anxiety. Today’s worries are cyber security, fake news, autonomous robotics and artificial intelligence (AI). Nothing special relates to Dec. 31, 2019.

A monster called social networking was created since Y2K. Its impactful “network effect” saw firms doubling their users in a couple of months. LinkedIn was founded in 2002 and Facebook in 2004, and the iPhone appeared in 2007. An old company like Google (1998) accelerated the amazing concept of the freemium business model. I neither fully anticipated the benefits nor the risks of being manipulated, addicted and giving up a good fraction of my time to the buzz. My 2019 New Year’s resolution is “selectively unsubscribe.” The return on investment thus far is excellent. The “fear of missing out” quickly subsided without need for anxiety drugs.

As a rule of thumb, I have long opined that medical innovations take a minimum of 20 years to come into widespread use. I use this loose rule to tweak my academic colleagues into considering reality when they write grants, papers and news releases.

I missed on many predictions of my own. I anticipated that by now we would have genetics as a significant factor in regular sessions with my primary care physician (PCP). Didn’t happen. Proteomics was coined in the mid-1990s, and it seemed clear that by 2020 there would be numerous approved in-vitro diagnostics tests based on the topic. Didn’t happen. I was very taken by therapeutic drug monitoring in 1980. Given that electronic health records (EHRs) were introduced decades ago, I anticipated that there would by now be clinical decision support systems that guide care with model-informed precision dosing. I saw dashboard prototypes. Didn’t happen, but the effort continues. In the 1990s, legislation was passed to encourage more inclusion of children in drug trials and the incentives have continued to evolve, with very little impact in practice. Wrong again. I anticipated that microneedle arrays would be in common use to introduce drugs transdermally with reduced pain. Didn’t happen. These are dreams not yet realized, but all remain works in process along with biosensors beyond glucose, microfluidics, peptidomics, lipidomics and metabolomics. Given this evidence, I’m upping my rule of thumb to 30 years.

We now seem farther away from the collective impact of “biomarkomics” on the standard of care.

There is also new thinking that never crossed my mind in Y2K. I’d never imagined that

hospitals would organize to produce their own generic drugs. It’s still early for moving the talking to the doing. That hospitals and pharma would be encouraged to reveal pricing has now just begun. That good idea will need refinement to overcome stubborn resistance and ambiguities. Amazon and Starbucks have transparency figured out.

Most drugs only treat symptoms, and that’s great for cash flow. The current promise of cures for chronic conditions can change the game. We’ve paid for drugs whether they worked or not. Paying for a promised cure that doesn’t come engenders the notion of money-back guarantees. With success, financing a cure over time the way we pay for houses, cars and furniture gets interesting (“20 years same as cash”). The concept of paying for outcomes vs. procedures sees a lot of ink, but not much more. At Y2K, immunology was far from my mind, particularly immunotherapy for oncology. Here we have a century-old idea made feasible by new tools probing deeper. Exciting, but overwhelmed with hyperbole.

A new reality is that my PCP dictates his observations and recommendations into an EHR system in the same way Alexa understands my inquiries about weather and sports. That took many decades, not two. That 3D printing (mid-1980s) can now be used to print dosage forms, replacement body parts and even organoids for drug discovery is cool beans. It’s early, but all three are a mission accomplished. Stem cell therapies and gene editing have also booked some early successes. Promises are realized narrowly thus far, but by Y2K+40 I suspect they can be a standard of care.

In his last column, Randy Willis expressed dismay at how quickly scientists can retreat from ideas that threaten the dogma. He used the concept of a central nervous system microbiome as an example. Microbiome as a name was coined in 2001. That there are little friends in our gut has been known for four centuries; that some may find a home in the brain is particularly exciting. It’s common to drop observations too early and hang with others too long. Given the place we are with treating Alzheimer’s, new approaches surely are needed and welcomed (Dominy et al. Science Advances, January 23, 2019; www.cortexyme.com).

In my own commercial R&D world, there are two advances I did not fully anticipate in Y2K. Automated serial phlebotomy from mice to humans is one, and ambient ionization mass spectrometry is the other. Both now approach 20 years, both have been proven in practice and yet are far from widespread adoption. I’m predicting Y2K+30.

What I thought would happen didn’t, and what I didn’t think would happen did. Biology is hard. I lose as a futurist, but approach Y2K+20 with optimism for the amazing breakthroughs from our DDNews readers, working hard for patients behind the increasing political noise.

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