Prime Slime

Working late in the lab, Dr. Lucian was proofreading a manuscript on his latest studies. His small office was beyond crowded, with books and folders stacked high on the counters. Buried underneath were a microwave and a small fridge. He ate most of his meals in the lab, like TV dinners and ready-to-eat packaged food.

A multi-component computer workstation dominated his desk. The extra large computer monitor was used to magnify images of bacteria from a microscope centrally located on his desk. The monitor was also used to televise news programs, sporting events, comedy shows, and the like. Evan lived in his office.

The office was also coveted for its air conditioner. His students called it the “cool” room, despite its drab, Navy-gray appearance. Evan’s office door led directly out to the lab, which in contrast was inhospitable in this heat.

After hours of editing, Evan took a long stretch, shut down the computer, and began to close the place down. Walking out to the lab, he noticed Dexter leaning over papers on his desk. Pleased to see someone so dedicated, Evan approached the graduate student.

“Let me show you a real monster.” Evan beckoned Dexter to follow him down the narrow aisle between lab benches. The outer walls were lined with black slate counter tops, and metal stools posed an obstacle course along the way. The lab was nondescript save for glass bottles on the bench tops and in cabinets, filled with colorful powders and liquids. The bright-colored bottles and dingy gray walls clashed like an unfinished painting. At the far end of the room stood a double-door, heated incubator used to grow bacteria. Evan opened it, pulled out a Petri dish, and brought the bacterial culture to a nearby sink as Dexter looked on. Evan nearly dropped the plate while lifting the lid, trying to avoid the dripping slime. The glistening green goo oozed in Technicolor.

“Jesus!” Dexter shouted, stepping back from the sink.

“Like I said, Dexter, bacteria are not wanting for slime.”

“That’s for sure!” Dexter exclaimed from a distance.

Evan, the veteran slime handler, neatly closed the lid and turned on the tap water to wash the slime down the sink. They watched with awe as the green slug slinked down the drain.

“Is that cool?” Dexter shrieked, concerned about the potential environmental effects.

“No problem,” Evan assured him, “just common, everyday bacteria already in the water system.” Evan sprayed alcohol down the sink to assuage his anxious student.

“Bacteria make tons of slime,” Dexter observed.

“That’s correct,” said Evan. “What else can you deduce?”

“Apparently…slime is not necessarily dangerous.”

“Exactly! Slime alone does not make a pathogen. Many other factors are involved in disease. In fact, too much slime can handicap bacteria. It can drain energy from other processes. Slime is an expensive commitment for microbes.”

The thought made Evan reflect on the costly commitments in his own life. After two failed marriages, he had been sucked down a drain or two, himself. Fortunately, most of the headaches and regrets lay behind him. The only real commitment left was to his invention. Bringing a product to the marketplace was one long haul, similar in many respects to raising a child. His brainchild was approaching maturity, but was not yet there.

Frankly, the job was far from finished, and Evan had grown weary. Never could he imagine the time and effort involved. Now, well on the other side of fifty, he didn’t have the grit to devote long days to it anymore. He was starting to smell the roses, and began entertaining possibilities outside the lab.

Fortunately, his invention had begun to attract attention. Other scientists and students were studying his agents for a variety of purposes. Evan was nearing the end of his usefulness, but many others had taken up the slack. With no interest in the detailed technical work ahead, and no acumen for business, he relied on others to bring the enterprise forward. Evan laid the egg and kept it warm for a while, but others would help it hatch and grow.

Evan knew it was time to step into a different role, to broaden his horizons, and become a more visible scientist. The success of his invention would propel him to a much higher level of credibility. He had faith in the process, and looked forward to reinventing himself.

Though not yet commercially successful, Evan was proud of what he’d done, and was especially pleased with his students. Science advances largely from the efforts of committed students. Under the tutelage of a master, bright young investigators are the engines of research. Attracting them was crucial, but it also took effort and patience to groom them. Evan recalled his own growing pains; how he tested a mentor or two in his time. By forgiving himself for his own mistake-ridden past, Evan cultivated patience toward his students. By raising a new crop of scientists, he honored the elders who nurtured him, and carried on the rich tradition.

Still waxing philosophical, Evan admonished his young student: “Speeding up the decay process would mean speeding up nature itself. Everything is synchronized to nature’s cycles. I don’t think it’s wise to interfere with these sacred relationships.”

“But Chief, the entire history of Western science rests on our exploitation of, and dominion over nature.”

“Maybe some mysteries are better left alone.”

“Still, I wonder what controls the decay rate.”

“There are many types of slime on earth, breaking down every conceivable thing - dead or alive - at different rates. There’s a slime for every purpose under heaven.” Evan’s twist on the biblical proverb went over Dexter’s head.

“Each slime process is different,” Dexter retorted, “but that does not stop us from manipulating one of those systems. Finding mutants that slow down or speed up infection and decay can tell us a great deal about the process.”

“So, how would you go about asking that question?” Evan inquired.

“Basically, we transfer pieces of DNA from your Kleb pathogen into a safe bacterial strain, and look for new traits, such as increased speed or increased slime production. These clones are not dangerous, so we can now study and manipulate these genes harmlessly. Thousands of genetically modified clones can be created in this manner. One or more of these mutants might prove interesting and cast light on the process of infection and decay.”

Evan considered Dexter’s proposal. Not wanting to seem like a Luddite, he tried to suppress any doubts. “I imagine it’s a worthy pursuit. But, I’m more than a little concerned. Genetically modified organisms, or GMOs, can be dangerous, especially using genes from that Kleb strain. You must consider all the consequences and adhere to federal guidelines.”

“Of course! This is not science-fiction, Chief. GMOs are created all the time in labs throughout the world. The probability of danger is near zero. The methods are foolproof. These creatures are nothing more than lab tools.”

“Yes, but I know bacteria,” Evan assured him. “A single clone can produce billions of offspring overnight. Dangerous germs can spread rapidly.”

“I hear your concern about safety, Chief. Yet, GMOs can be constructed to pose no hazard. I don’t see a problem. And, if necessary…we have MIFF.”

Evan paused. “If you want to play, my lab is at your disposal. Order what you need. I’m curious to see what you come up with. But first you should know all the regulatory rules on cloning.

“I’m on that, Chief.”

“You should also read up on all aspects of slime and disease, including quorum sensing.”

“Quorum sensing?”

“Yes, bacteria communicate with each other by releasing chemical signals. When a quorum is attained, bacteria begin to talk to each other.”

“What do they talk about?”

“They make group decisions regarding how to grow together. Bacteria were the world’s first architects.”

“That’s wild! I’ll check it out immediately!” And with that, Dexter ran to the cool room and searched for “quorum sensing”. He was surprised to receive thousands of hits.

“Good luck, Dexter.” Evan left the building, heading for home, his mind a bit troubled. Theoretically, Dexter’s project made sense. This Kleb strain provided a unique opportunity for them to delve deeply into the nature of things, and to solve important problems in biology. However, nature might not comply so easily. Decay happens the way it happens, and there is a reason for it. ‘There’s a price to pay for speeding decay’, Evan thought. It was catchy, but also scary.

Every encounter with Dexter was a challenge. It was not Evan’s wish to discourage the young man’s passion. He had little choice but to yield to his gifted student and to the future of science. There was likely no harm in it, as long as Dexter played by the rules. Why not delve into some molecular biology and start competing with the gene jockeys of the world? This is where science was headed anyway. Dexter could take Evan’s research into the 21st Century and improve their chances of procuring grant support. And, if something went wrong, MIFF could very well prove useful. Evan waxed heroic about putting it to use.

Genetic mutation is not an invention, but rather nature’s intention. Mutations occur frequently, especially among fast growing creatures like bacteria. Bacteria can reproduce several times per hour, which increases the chances for genetic error. Though most mutations are not useful and often lethal, they are essential to insuring diversity and adaptability in a population. Without mutation, evolution could not proceed.

Unlike the random, haphazard mutations in nature, genes can be mutated with precision in the lab. Single-point mutations can be created in specific genes for specific purposes. Such mutations could completely destroy a gene, or modify its activity. To ensure safety, such mutations are made in “safe” bacteria, unable to thrive outside the lab. The E. coli bacteria used for these purposes died instantly when exposed to sunlight. They are also weakened in other ways to prevent disease spread. With all these mechanisms for precision and safety, Evan had to trust the new technology.

Though not a geneticist, Evan Lucian was becoming known worldwide for his pioneering work, and as a shining star at Burrstone. Indeed, there were many good scientists at this institution, along with a cadre of good physicians. What made Burrstone so special was the interaction between scientists and clinicians. The Medical Center had built a reputation upon bridging its basic and clinical sciences. That’s where Drs. Lucian and Wally intersected. Clinicians like Wally identified and treated problems, while scientists like Lucian unraveled their secrets and created solutions. In this strategic overlap, Evan’s drug was being developed for clinical use. Among the Institution’s many patents, none was more promising than MIFF.

Evan was slowly warming to the idea of commercial success. It justified decades of work, and brought some respect to his efforts. Success also promised to free him from the work-a-day world. Research had its moments, but required sacrifices he was no longer willing to make. After a lifetime studying slime, he looked forward to other things, like finishing long neglected projects, traveling, or entertaining other passions. There comes a time in life, and in one’s career, to move on to the next level, to free oneself up a bit, and take on more administrative and advisory roles. It was time to delegate the grunt work and unending experimentation to energetic students, and join a broader conversation in science and beyond.

To aid the process, Evan had become the best recruiter on the faculty. Many students took on projects in his lab over the years. Depending on their career path, students committed from months to years in research. High school students and undergraduates managed summer projects, and medical students took on semester stints. Short-term students were often more a hindrance than an asset. It took a whole semester just to learn the lab basics. So, Evan learned to expect nothing, and to endure their tenure stoically. It was part of the job. The real prize was in attracting high-quality graduate students, who would spend years committed to his work.

The legacy of science depends on delegating good ideas to good students, and letting them take it to the next level. For Evan, the task wasn’t easy. Yet, with a new appreciation for biofilms, a promising anti-biofilm agent, and his growing stature, things were moving in his favor. With these powerful magnets for attracting good students, Evan nabbed two of the best. Brilliant students like Terri and Dexter took on long-term projects, and spent most of their time conducting research. Unlike besieged medical students, they could immerse themselves deeply into theory and methodology, and focus intensely on a single problem. Graduate students are the nuts and bolts of scientific progress.

Evan’s new students were aware of the great potential of his anti-slime agent. At low concentrations, MIFF prevented slime without killing anything. Essentially it rendered bacteria naked, unable to stick to surfaces, and easily washed away, swallowed, or flushed. MIFF disarmed disease without harming life. Antibiotics and biocides, in contrast, are designed to kill, and cause considerable collateral damage. By preventing bacterial stickiness, MIFF thwarted infection and decay without damaging life.

It was a fairly simple and clean, as inventions go. MIFF was a natural substance made by a fungus. It worked at concentrations 100s of times lower than other competitive agents. Plus, it did not linger, but broke down into harmless matter over time. MIFF promised to be the perfect alternative to wasteful, toxic biocides.

MIFF was a major breakthrough for many reasons. Yet, there were still several problems that had to be ironed out. First and foremost was its foul odor, which stood directly in the way of general usage. No one would want to use something that smelled so foul. It was also not yet tested in humans. Major drug companies were not going to commercialize Evan’s agent until it was proven safe, not to mention fully deodorized. Drug companies were also reluctant to develop new technologies, which angered Evan to no end.

“Does your invention make you stink?” asked a pretty lady in the front row.

“That smell could kill a moose,” said another.

For the millionth time, Evan tried to explain: “MIFF contains sulfur, and everyone knows what that smells like. However, we believe that the smell can be largely removed. My students are working on that.” Evan pointed to Terri and Dexter proudly.

That was good news for those living on campus. Every new batch of MIFF went out the door with a bang. The smell could not be contained, even under a chemical hood. Students avoided walking near Evan’s lab, whenever possible.

“You expect people to take that stuff?” asked another student. “That’s like guzzling Mr. Clean!”

“Very funny,” Evan responded. “Obviously, more work needs to be done in animals before it is ready.” The hiss of displeasure was heard from many of his female students.

“I don’t like experimenting on animals any more than you do!” Evan’s face flushed a dark red. “We are doing our best to minimize animal use. We restrict our studies to rodents, minimize the number of animals used, and reduce the pain and suffering involved whenever possible.” He was acutely aware of the volatility of the animal rights issue. Fortunately, another student changed the topic.

“Why not make MIFF gel capsules? That’s how they make garlic pills odorless.”

“Good idea!” Dexter blurted. “MIFF could be taken on trips to prevent traveler’s diarrhea. It could also be used to deodorize colostomy bags.” As usual, Dexter was much too graphic.

“No shit, Sherlock!” Burt Nadley shouted from the back of the room. “It might also give you bad gas.”

A student near the front asked earnestly: “Excuse me, Dr. Lucian, could you repeat how MIFF works?”

Evan smiled encouragingly as he tried to simplify it further. “Let’s put it this way: minerals and sulfur go together. MIFF is a sulfur compound that enters bacteria and ties up certain minerals. Some of these essential minerals, like iron for example, are involved in making slime. So MIFF mucks up the slime making machinery inside bacteria. Does that make sense?” Some of the students still looked puzzled, but the illustrations on the blackboard helped considerably.

“Is MIFF toxic to human cells as well?” Terri asked.

“Yes, at higher amounts,” Evan admitted. “Fortunately the anti-slime effect occurs at low, nontoxic levels. Anything will kill you at high enough concentrations, even water!”

The unique property of MIFF was its anti-biofilm activity. Without slime, bacteria cannot avoid antibiotics or white blood cells, and cannot stick to surfaces. Slime retains water to protect bacteria from drought, and traps nutrients. It is multi-functional: a camouflage, shield, adhesive and scavenger, all in one. That’s why it’s so abundant in nature, and why MIFF was so effective.

Evan continued. “Doctors rely heavily on antibiotics to treat infections. However, biofilms are highly resistant to antibiotics. Newer, smarter drugs like MIFF are needed to stem infections and reduce our use of antibiotics.”

“Prevention is good,” Dexter pointed out, “but what if slime is already formed? What about treating a full-blown infection?”

“Once slime forms, more MIFF is required, which increases the potential for toxicity. There is no perfect drug in that case. Like they say, an ounce of prevention is worth a pound of treatment. Still, MIFF may be the drug of choice at all stages of infection.”

Unfortunately, prevention was a hard sell in the industry. Treatment was preferred above prevention, since more drug could be sold, resulting in larger profit margins. Indeed, many medical specialties and services would fade if disease was prevented, not to mention lower health care costs. The disease industry had become institutionalized, and stock holders were making fortunes on the backs of the sick. Funds for prevention research were hard to come by, either from federal or private sources. Evan’s search for financial backing was most frustrating. A great invention was no promise of success. The cards were stacked against him.

In spite of all the resistance, Evan spent much of his time submitting proposals for funding studies in medicine, dentistry, agriculture and industry. He promoted MIFF as a disinfectant, antiseptic, antibiotic, and preservative. He approached any company that could conceivably incorporate MIFF into their products, such as in toothpaste, antibacterial soap, detergent, paint, or as a food preservative. MIFF was potentially useful for water treatment, plant disease, and many other applications. Biomaterial scientists could coat a variety of materials with MIFF, such as catheters, plastics and filtering devices. It was being evaluated around the world for one purpose or another.

A big part of Evan’s job was to make the world aware of MIFF’s potential. As such, he found himself wearing a number of hats, many of which did not fit so well. Going from the research lab to the marketplace was not easy. His diplomacy skills were lacking, and his business acumen rudimentary. After a number of early mistakes, Evan delegated MIFF development and technology transfer to the new legal team at Burrstone.

Drug development was also about secrecy and restraint. One slip of the tongue or pen could ruin patent protection. But this ran against every instinct that scientists like Evan lived by. The only way he knew how to grow the science was through openness.

Evan also discovered how fragile business relationships were. One emotional outburst could destroy a promising connection. The time had come to evolve, and learn patience and diplomacy, if he planned to gain from his invention. Developing MIFF became a lesson in emotional maturity.

Success summons opportunities for growth, both materially and spiritually. Change is inevitable as one gets swooped up into something bigger than oneself. Insight comes with every obstacle, every rejection. One has to learn to deal more effectively, to master new realms of being. To grow in business, one has to accept the reality of an unfair world, and detach from outcomes. At the same time, one must stay largely within the bounds of his or her expertise. Inevitably, the learning curve gets much steeper.

Evan’s habit of disclosing information about MIFF did not sit well with hospital officials, since the methods and composition of his invention were strictly confidential. Evan’s openness could easily have diluted Burrstone’s legal rights. The patent lawyers urged him not to discuss the composition of MIFF. In the past, Evan had damaged his financial position by being too forthright. But this time around he was learning a valuable lesson. The ticket to success was in keeping your mouth shut, and getting others to do the dirty work.

With one painful lesson after another, Evan stumbled along, but kept moving forward. Being impatient and exuberant did not cut it in the business world. Despite his lofty academic position, he was still a work in progress.