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GLOBAL INNOVATION

Fusion Series

How World Class Innovators Create the Unexpected

Killer Mystery Infections and the 24-in-1 Test

10 Million+ Lives & USD 1.2 Billion to Save Worldwide

 

 

The Fusion Series Part 5: Fusing

Dr. Ravi Kumar Banda and his team created the world’s first life-saving fusion of 24 different bacterial, fungal, parasitic, and viral diagnostic tests

“Hey, Ravi — there’s something unusual here we can’t figure out. Are you free to come?”

Ravi hopped on his scooter and raced over.

“What did I miss?”

“Nothing. I waited for you. You’re irrationally enthusiastic — you realise that, don’t you?”

“I prefer to call it curious and thoughtful. In fact, I keep thinking about what we found last time — tuberculosis of the brain — and how the autopsy showed the bacteria that causes typhoid instead caused meningitis. You know, these people wouldn’t have to die if we could diagnose these infections in time. I mean, everything we’ve seen is treatable.”

“I know. That’s exactly why I’m always calling you for autopsies. I realize your research is on schizophrenia and the bio-chemical aspects of drug receptors, but other people in the US can do that. With our access to tissue samples, diagnosing the undiagnosable needs to be done here in India — by someone with your kind of curiosity and enthusiasm.”

Diagnosing the New

Dr. Ravi Kumar Banda (the scooter rider with insatiable curiosity) trained as a medical clinician and then earned a diploma in psychiatric medicine. He switched back to basic science (psychiatric biology) to investigate one of the causes of mental illness — chemical brain damage. He moved to Bangalore, India to do his PhD research on drug receptors and studied foetal and early-childhood brains, befriending a pathologist along the way.

The problem of failed diagnoses rooted in the back of his mind.

Post-PhD, at the end of 1995, Ravi founded a lab at XCyton to develop a diagnostic test for a newly-codified and dangerous infection: HIV. Scientists were just discovering that HIV has different subtypes, and one of these — HIV 1C — was found in India. Scientists guessed that it might represent up to 68% of India’s HIV cases.

The diagnostic kits from the US were not only expensive, but they were also based on the most prevalent subtypes in the US — HIV 1A and 1B — with a significantly-different protein structure.

Ravi believed India needed locally-made diagnostics that were not only more cost-effective but were also more appropriate for the market. He developed a kit based on synthetic proteins (simpler to produce than natural) which diagnosed Indian HIV more cheaply and accurately.

“If something is very complicated (like natural protein production for HIV diagnostics), that’s where you can make a difference. If something is easy, anybody will do it.”

The World Health Organization (WHO) approved the product, and it was well received. Scientists later discovered that HIV 1C actually represented 98% of India’s HIV — not 68%.

Despite the importance of a locally-developed test for the locally-found strain, it didn’t sell well, because 70% of the market requirement was from Government. They had unwieldy procurement procedures, and Ravi found it harder to push forward bureaucracy than the boundaries of science.

Nonetheless, Ravi and his team kept moving forward and developed a diagnostic kit for Hepatitis C. At the request of the Bill & Melinda Gates Foundation, they created another for Japanese Encephalitis, which was procured by WHO.

In 2004, XCyton was well-established, growing, and had 38 investors.

Diagnosing the “Undiagnosable”

A conservative businessman would have built on their established successes, developing incremental, routine improvements on diagnostic processes and producing less-expensive, local diagnostic kits. However, Ravi wanted to do a 180-degree turn and create something new.

His dream was to work in Critical Care and save lives.

Ravi knew Critical Care had its problems. When people die in hospital, 60–80% of them do not die of the disease they were admitted for. They die of infection — mostly hospital-acquired infections that take advantage of the patient’s suppressed immune system. Death certificates show “kidney failure” even though the cause is infection. When bacteria enter the bloodstream (sepsis), all parts of the body can be damaged — kidneys, liver, lungs, brain. The result is called “multi-organ dysfunction.”

Sepsis death rates worldwide are 40–60%, and in only 12–15% of cases are the causative bugs actually diagnosed. Doctors around the world treat such patients via guesswork 70% — 85% of the time. Patients can die from either the infection itself or their own immune response in later stages.

Without knowing the exact cause of an infection, doctors prescribe an expensive cocktail of antibiotics (“empirical therapy”) while sequentially performing diagnostic tests — struggling with bacterial cultures that provide a result only 10%-15% of the time. Antibiotic cocktails can cost USD 7,500–9,000 per patient — way beyond the means of most Indian families, 85% of whom have no health insurance. And while tests are being conducted, sepsis progresses.

Ravi discussed his dream of diagnosing sepsis with friends and funders, estimating development costs at USD 1.7 million. None of his individual funders could provide that much, but they were powerful people with high-level connections. They decided to pursue it.

One of the group — a director of the Institute of Science — was absent from an investor meeting and called the others. When told of their ambitious desire, he responded,

“Are you mad? He has no money, and he’ll pursue his passion and kill himself. Do NOT do this!”

Ravi met him for coffee that afternoon and reminded him,

“If a cause is profound, means will follow. Everyone says it’ll fail and I’m being foolish, but I don’t mind being foolish. So, what?”

The director was still against over-ambitious projects but said he would recommend Ravi to everyone he knew. If anyone could do this, Ravi could.

 

First Prove Yourself on Something Else

Before launching into the sepsis project, Ravi would have to prove himself on a newly-launched initiative by the government’s Disability Commission. Each year, 200,000 people were going blind because of infections, and the Council for Scientific and Industrial Research (CSIR) would have to do something about it.

CSIR’s Director General, Dr. Mashelkar, called the nation’s top eye hospitals for input, alonside CSIR’s Director of Technology Networking and Business Development (TNBD), Dr D. Yogeswara Rao (also In charge of their New Millennium Indian Technological Leadership Program). They asked who could develop a test and make it commercially available, immediately. The TNBD Director recommended Ravi, and several committee members knew Ravi and were excited to work with him. Ravi met with them.

The DG asked how many months it would take to develop the eye kit, how many kits he could produce, where he would raise money for marketing, plans to take it abroad, etc. Ravi agreed to discuss all the issues and more but first presented his thoughts on critical infections, letting them know that the eye diagnostics shouldn’t be done with serial testing any more than sepsis diagnosis should.

They needed an integrated test (for all relevant pathogens at once) so patients would not lose their sight during the testing process.

Ravi agreed to work on it, but since it had never been done before, he wanted the time frame of three years instead of two. He was confident it could be done but was not sure of the final form of the product. Providing accurate diagnosis was the most important feature and could not be compromised. However, all other product specifications were negotiable. He was willing to fail if it couldn’t be done. It was a journey of discovery.

The Director General agreed, saying,

“This is a project worth failing. The country will learn something. And for the very first time, I’ve found a guy who says he’ll put his head on the chopping board if things go wrong. I’ve never found one before. Now that I have, I’ll give him the money.”

He funded the partnering institutes with grants but funded Ravi with a loan and a contingency fund he could ask for (with explanation). He wanted a progress update every 6 months, and with each update, they discussed, resolved problems, and Ravi received whatever support he asked for.

Three years later, the eye-infection diagnostic test was done.

Ravi reminded the Director General in 2008 (after a new DG took over) that the eye test was a proof-of-concept for integrated diagnostics. Now it was time to develop a test that would diagnose the pathogens causing sepsis. The test would be used to detect pathogens after a clinical diagnosis of sepsis.

The project was granted after going through three committees and a lot of deliberation at both scientific and financial levels.

 

Save Us from Sepsis

By 2005/2006, XCyton was in financial turmoil. Nonetheless, Ravi and his dedicated team of insatiably-curious scientists would experiment in the lab until evening; then brainstorm over tea, biscuits, and Maggi noodles; and then experiment some more, late into the night.

It was devilishly difficult to integrate bacterial, fungal, parasitic and viral diagnosis into one test. They were told by a lot of well-meaning friends in the scientific community that it couldn’t be done.

However, they kept moving forward, financially and scientifically, day by day. Test development for sepsis prevention took nearly four years, from early 2008 to early 2012 and cost USD 7 million. They were never really sure if it could be done or not, as the product had presented them with apparently-insurmountable technical problems. They despaired that their dream product was probably not feasible, after all. It was an incessant spirit of “resurrection” that moved the product through these difficult stages.

At last the test was done, and within three years, they processed 10,000 patient diagnoses (15,000 to date). XCyton’s test is a multiplex PCR (polymerase chain reaction) test directly detecting virulent pathogens — definitive diagnostics of individual species (bacterial, fungal, parasitic, and viral), as well as antibiotic resistance. After a doctor takes blood, eye fluid, brain fluid, etc. and sends it (overnight express) to XCyton, the lab processes it in 7 hours and responds via phone/email — within 24 hours of a patient entering hospital.

While searching for something else on the Internet, they discovered 14 publications on the efficacy of their approach. The data shows that XCyton provides the highest sensitivity and specificity of any approach dealing with sepsis. XCyton is encouraging another 15 studies, providing data and analysis needed for international journals.

In one such study, using the XCyton test reduced mortality among neonatal sepsis cases by 83% (from 18% to 3%). Instead of accurate diagnosis and treatment only 15% of the time, patients can now expect diagnosis and treatment 72% of the time. Ravi and his team believe they can increase the rate of detection to 85% by instituting a hospital protocol to take a sample and send it for testing as soon as a patient with critical infection is admitted.

Integrated testing also reduced hospitalisation by 4 days, reduced time on ventilators, and reduced anti-biotic use by half. It performed well on every parameter.

In India, 800,000 new born babies die each year, of which 80% are from undiagnosed infections. XCyton data suggests that 80% of them can be saved — over 500,000 lives per year. Ravi and his team are doing a study at a hospital that did make the test a standard protocol for all sepsis patients at the time of admission. The resident physician reports having seen at least a 70% reduction in mortality.

An additional 3.5 million non-newborn patients in India need the test each year and face a 48% mortality rate. Even if the new test saved only half of them, that would be 840,000 lives saved.

With 19 people dying from sepsis every minute worldwide, 10 million lives a year could be saved from sepsis alone. Further, antibiotic use could be reduced by USD 225 million annually in India — over USD 1.2 billion worldwide.

Global expansion is now their first priority, as part of ImmunoHeal Personalised Medicine, a new health-sciences corporation based in Malaysia. The next step for XCyton is to automate the testing process, and they’ve already commenced that 2-year (expected) project.

 

Inward Openness & Inspiration

What sort of a man would hop on a scooter to assist in an autopsy that’s not in his research area? Or integrate knowledge from a collection of specialties in order to integrate bacterial, fungal, and viral diagnoses?

Ravi comes from a highly-conservative, very open-minded Hindu family with extreme empathy and internal drive. His father taught him that,

“Whatever you work for, the work is the fruit — not school marks or money or anything else. So many scientists have done things of great difficulty and brought it to the world. Why? It all came from something within themselves that nothing outside could stop. Those that never came to fruition were because of personal shortcomings of individuals. At the end of the day, you must overcome something within yourself to bring a new creation to the world.”

Both parents taught sensitivity to human values, not narrow, religious values. Ravi is a devout Hindu and practices the rituals of his faith. His daughter-in-law is a devout Christian, and they get along beautifully, since they are both deeply faithful.

Ravi combines his meditation and exercise, spending at least 1–1/2 hours a day chanting on his cross-leg trainer (designed for Yoga or muscle training). Missing a day or two drives him nuts. The drive to office with his wife is non-talking time — himself chanting and her sitting quietly.

Such inward openness can be instrumental in problem-solving, as when Ravi saw the solution to a problem in a dream:

“We purchased this huge microscope at the Astra Research Centre in India, and it wasn’t taking good pictures. We needed a much higher speed. 400ASA pictures had to be taken, and we would have to call the manufacturer the next day for help. I went home and slept. In my dream, I clearly saw on the side that there’s a switch for 400ASA. Next morning, I ran there. I didn’t even have my coffee and bath — I just ran there. At the side was a small plate. We opened it, and inside there was a switch. I put the switch to 400ASA and took the pictures. I’d flipped through the manual earlier not noticing anything in particular, but somewhere, somehow, the information registered. Dreaming can be very useful for solving problems.”

Outward Openness, Sensing, and Empathy

Ravi accepts people as they are, talking with and listening to everyone in his company. He’s interested in all of life and science, including a broad array of interests like bio-fertilizer nitrogen fixation, the development of flower colour patterns, and the compound eye of the colour-blind honey bee.

He’s not a great noticer in general but does care deeply for people. He’s immediately aware of employees’ feelings, shows care and concern for what’s happening in their personal lives, and mentors and counsels them well beyond their scientific duties. The moment he walks in, he can tell how someone’s feeling by the way he’s greeted. XCyton staff have learned a special way of life: no one hides anything. Ravi mentors them all and cares for both their work and their personal well-being.

Ravi manages by consensus and develops intrapreneurship among his staff. On one occasion, he returned from a trip seeking a big order with the government, and an employee stopped him at the door, asking what happened. He explained and listened and was later asked by someone else, “Why are you explaining your activities to the man at the door? Who’s he to question what you’re doing?” Ravi replied that the man’s interest means everything to what they all do — he’s a company stakeholder taking ownership, which is a good thing. Ravi can’t speak the language of the cleaning staff, so asked his wife (an executive in the company) to be their connection and share with him what she feels should be shared.

Ravi pays no attention to status. He listens to everyone with respect and interest in their ideas. He fears it may be a defect, as a businessman, to be so very interested in people’s lives and the deeper meaning behind what people say.

Not only does he see from others’ perspectives (cognitive empathy) and pick up on their emotions (emotional empathy), but he also takes action (active empathy). He gives generously of his time and money to help, despite the lack of abundance of both.

On one occasion, a colleague’s father had a throat problem, and Ravi sent him to a surgeon friend. The surgeon called back and said it was cancer. The colleague didn’t understand all the treatments and options, so Ravi took time off, met the doctor, and returned with the information. The son and father chose to let the advanced-stage cancer take its course, and Ravi kept in touch with the situation. When the father needed help — at 2am or any time — father and son would call Ravi (who lived quite a distance away) to come and help. Such caring is available to everyone at XCyton. Ravi is the “first line” of medical assistance.

Ravi describes XCyton as a family of 38 people — very loyal staff who care about the business and do so much more than their jobs. On a festival day in a deluge, for example, one of the staff left his family celebration to fix the drains at work. When financial difficulties erupted, everyone stayed and said they were willing to take a 50% pay cut for 6 months to stabilise the company. When asked, “Is it worth it? Why do you stick to it?” Ravi said,

“What makes it worthwhile is the people. I’m very lucky with people. That’s my major capital. Lots of them stay with me for long periods of time, and there’s always people who come and help me, from very unexpected quarters.”

Perhaps it’s not a defect to pay attention to meaning and motivation — to care and show compassion.

Collecting

He’s a great listener and gains information mainly from people — asking questions, going to talks, and picking up far more than the average listener. He believes everyone has something to teach. He collects people and even stays in touch with his old teachers. With a huge network, no matter what the topic, he has a friend who knows something about it.

“His scientific knowledge is vast, and the best qualities I’ve seen in him are his questioning, thinking, and willingness to make mistakes — also supporting ours. According to him, there are no stupid questions, and when you learn from your mistakes, you’ll grow.” 
- Sunil Govekar, XCyton Head Scientist

Ravi is noted for love of a challenge, joviality, child-like qualities, openness to feedback, openly sharing what’s on his mind, capacity for change, flexibility, and an elephantine memory. He prefers textbooks to google and cares most for how his creations would be useful to human kind, not his own monetary advancement. It would be very easy for him to open one more lab in the building for blood glucose or some other easy money-maker. But he won’t do it unless it’s a challenge that affects everyone.

“I think it’s his heart that makes him work, not business results or even the intellectual kick of scientific advancement. It’s the heart — what can he do for someone else.”
 — Latha Lakshman, XCyton Chief Operating Officer and wife

At the end of the day, Ravi seeks happiness, and creating good in the world makes him happy. Ravi’s leadership is neither purely business-driven nor science-driven. It’s humanity-driven, enabled by both business and science.

 

Fusing

Did integration create value? Yes. Separate, sequential bacterial, fungal, and viral tests already existed. Integrating them can save over 10 million lives (for sepsis alone) and USD 1.2 billion a year — value arising purely from integration.

What’s shocking? That less than four years of effort and USD 7 million of investment could turn into USD 1.2 Billion of value created per year (for sepsis alone).

Is the value of fusion predictable? When it’s a radical new innovation, generally no — there’s not enough information at the start. But with experimentation and experience, his HIV team (for example) learned that HIV 1C in India surpassed early estimates of 68% incidence, representing instead 98%. Only after the sepsis test was well underway could they believe it would succeed and start estimating what (and whom) it could save.

What was necessary to make it happen? First, Ravi and his team had a track record of success (HIV), but instead of the usual way business is run, making incremental improvements on successful activities, Ravi chose a new direction, seeking radical innovation — not routine. He had to assume substantial risk (accepting loan funding instead of grants offered to the institutes), and he had to be willing to fail (“So, what?”), especially while leaders in the sciences pronounced it impossible.

Further, the project he wanted to work on (sepsis) had to be put on hold while he developed a proof-of-concept for another problem that already had a solution mandate (eye infections). They had to sustain their momentum.

Pursuing the currently-impossible had to be managed differently from business-as-usual. He declared it a journey of discovery and conducted progress checks every 6 months, not promises of results he couldn’t predict. Success would take years, breadth of knowledge and connections, and an integrated, dedicated team of scientists who bring their whole selves to work, integrating “work” and “life.”

Integration is necessary to produce an integration.

Finally, it had to be a project worth failing — high impact, offering important learning no matter what the result. Difficulty should be expected.

After all, if it were easy, anyone would do it. It would require irrational enthusiasm.

Are you irrationally enthusiastic about something?
Is it high-value, difficult, and offers learning with either success or failure?
Does it require a new, integrated approach?
Will you hop on a scooter at a moment’s notice to do it?
fusioneer
ˈfjuːʒ(ə)nɪə/
noun
1. one who innovates across domains of industry, field, country, social class, etc.
◦ s radical innovator, interdisciplinary creator, T-shaped person, borderless freethinker, boundary-crossing integrator, oddball;

Dr. Ravi Kumar Banda is the Founder of XCyton Diagnostics and is from India. For more information on his work, see: LinkedIn and XCyton.

I thank the participants in this study (Fusioneers and Friends) for your insights, sharing, help, and patience. You inspire me, and I am honoured to know you. Special thanks go to Gladys Lee for her marketing excellence and video- and podcast-production brilliance, as well as the host of creative professionals involved in producing the videos and podcasts (you’re all listed on YouTube, iTunes, etc.). I extend a warm thanks to Fusion Research Assistant Dr. Lee Poh Chin for her continually-wise and dedicated contribution to this research, as well as i2i Executive Shareff Uthuman for managing the rats-nest of global research travel and budgets. I thank Nitish Jain and the S P Jain School of Global Management for supporting this research — you’re the foundation that enables the whole project. You are all God-sends. It takes a village to write a paper.

Photo/video cuts courtesy of Dr. Ravi Kumar Banda, Depositphotos, and our own creative team.

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