Another draft of
The Invention Adventure-1                                           Ken Rubenstein

        It’s 1970 as this New Jersey-born lad basks in Palo Alto’s fine rendition of early-autumn weather. How did I get there? Let’s just say the story resembles Jerry Garcia’s long strange trip.

Starting with a relatively uneventful four year stint at Passaic High School,  I sailed into Rutgers University’s New Brunswick campus as a chemistry major, and skidded right back out 18 months later to avoid the embarrassment of inevitable dismissal. I next took a modest step down in prestige, rejoined my parents’ home, and enrolled in nearby Fairleigh Dickinson University, then commuter college with an iffy reputation. Bearing down hard, I managed by 1962 to graduate in with honors in chemistry. Fortune reigned then as our government struggled to gain ground against the USSR in the post-Sputnik era. They had set aside ample funds to encourage graduate training of scientists and engineers. And so I landed a fully paid slot in the University of Wisconsin’s organic chemistry doctoral program with enough income to cover living expenses.

         On graduation four years later I found myself a recipient of more job offers than I’d ever dreamed possible. I’d married an aspiring librarian, Joyce, at whose urging I took on the role of research chemist at suburban Philadelphia’s Rohm and Haas Company. After eighteen months I realized that working on  improved permanent press fabrics and better-adhering paints lacked sufficient pizzazz to keep me awake and switched on.

         I explored possible next steps and decided on approaching a noted biochemistry professor across town at the University of Pennsylvania. He proved willing to fund me for two years of post-doctoral life sciences learning, while doing research in his lab. In return I’d use my chemical skills to cook him up a few compounds he couldn’t buy on the market.

         By 1970, two hard but productive, years later I was ready once more to leave the groves of academy for an actual job. Guess what? With all those PhDs the feds had minted in the 1960s, American companies found themselves over-full of bushy-tailed Ph.D.’s, and not a single interview came my way. In need, I tapped my network of Wisconsin alumni and came up with a single promising offer as a post-doc at a small start-up venture in Palo Alto. They planned that year to hire four such temps, only one of which would earn a coveted permanent post there—at Syva Company, a joint venture of Syntex Pharmaceuticals, originator of the birth control pill, and Varian, a cutting-edge instrument manufacturer. Syva was tiny, my badge bore number 13.

         My bride and I journeyed west, and took up residence in a Mountain View apartment with a splendid view of the Southern Pacific Railroad tracks. My work-home in the Stanford Industrial Park was a compact building at 3221 Porter Drive with three labs, six offices, a big old live oak on the lawn, and grassy space out back with a picnic table for lunches. I spent most of my time at Syva in a lab shared with three chemists and a manager named Richard, a smart ambitious German immigrant who’d recently completed a post-doc stint at UCLA.

I soldiered on, dispiritedly, synthesizing molecules for our new drug abuse detection system, with no opportunity to use my hard-won biological knowledge. I’d also learned that said system had a major flaw. Test samples containing lots of vitamin C gave invalid results. Nonetheless, our test to detect heroin in urine went live in Vietnam where GIs joked about having to visit the Pee House of the August Moon.

The test method met the Silicon Valley mantra, “Faster, cheaper, better.” A minimally-trained operator could run a test in a minute versus the traditional method which required skilled techs and took half an hour per sample. Still, with all those advantages we needed something better to address broader applications.

One October morning as I beavered away at the bench, Ted, our research director zoomed past me headed for Richard’s office. Short, bald, trim, goateed, and ever the dedicated scientist, he often whizzed about. Today, he had an extra gleam in his eye. I saw him through the glass office door gesturing excitedly at Richard, who in turn seemed a bit light on enthusiasm.

Ted left, and Richard called me in. He explained that Ted had just presented another of his schemes for building a better test system, and hadn’t yet been able to interest any his chemists to work on it. The idea required using an enzyme, about which most chemists didn’t know much.

Two things got adrenaline my flowing. First, I desperately wanted to lengthen my one-year appointment into a permanent job. Second, by virtue of my stint at Penn, I was pretty familiar with enzymes. So I volunteered.

Syva had a nice little chemistry library, but not good enough for this search. I spent the next five days at our parent company’s pharmaceutical library looking through books  and heavy bound journal volumes for just the right enzyme needed to bring Ted’s idea to life. It had to have a chemical handle adjacent to where the enzyme did its catalytic work and to which I’d attach our test molecule.

On day five, I found a book that had a picture of an enzyme called lysozyme. A flash of energy ran through my nervous system when I realized that it had just right layout to do what I want. On top of that, I’d used lysozyme often in my post-doc work at Penn to chew up bacteria and release their innards. Thrilled big time, I ran back to the lab and ordered up the fixings.

On receiving them I began work trying to assemble a prototype test. A week into the project, I was amazed and delighted to find that I actually had one. My manager, Richard, congratulated me and generously suggested I go solo to show my results to big boss Ted.

He was exhilarated, to say the least, and my status in the company took a sharp upturn. Those two weeks of library and lab work triggered Syva’s expansion during ten years from 45 employees to more than 1,500 and annual sales in excess of $400 million. I got my permanent job and served in various lab and management positions during a 13 year tenure.

More importantly from my perspective, the test method, soon given the acronym EMIT, enabled a major advance in clinical lab technology. High sensitivity technologies available then used unstable radioactive isotopes and were awkward to automate. EMIT circumvented those problems and gave results in minutes using automated or manual instruments already found in hospital and commercial labs.

During the next year I worked on improving EMIT and assisting in development of tests for abused drugs in urine. Methadone maintenance centers and hospital emergency labs became good customers, and sales climbed. EMIT’s success left me feeling good about the scientific achievement, but not super stoked by its application.

For several reasons, including our proximity to Stanford, Syva had access to an exceptionally bright group of consultants. One of them suggested we bring on another. Charles Pippenger, a down-home whip-smart Indiana-bred pharmacologist from Columbia Presbyterian Medical Center, flew to Palo Alto and convinced us that EMIT should be used for therapeutic drug monitoring. Abbreviated TDM, this meant measuring blood levels of drugs that people took for certain chronic conditions. Since people metabolize drugs at varying rates, patients given a standard could end up under- or overdosed, sometimes dangerously so.

Up to then, labs couldn’t do much testing because the work was so specialized and slow. Pipp, as he liked to be called, felt that EMIT would be a perfect fit. He convinced us, and we set about implementing his recommendations, initially for two anti-epileptic drugs, Dilantin(R) and phenobarbital. 

Development proceeded well for six months before running into a major stumbling block. Getting good results seemed to depend on who was running the tests. I was asked to come over and help. It turned out that the lead chemist, frustrated by the problems, had falsified results. An engineer and I tracked the glitch down to a fluid transfer mechanical issue. 

Back in the groove, we gave Pipp pilot reagents to take back east. He soon visited us, reported that the tests worked well in practice, and that he’d saved a child’s life by quickly pinning down in minutes that the problem was too much drug in the blood rather than something else. For the first time, I came away feeling super-stoked about what we’d accomplished.