1

STANDING ON THE FIRST TEE

I was standing on the tee box at the first hole. A par five. A pond on

the right, trees and rough on the left. A bunker about 200 yards

ahead. I couldn’t see the flag.

It had been over a year since I’d picked up my golf bag. A set of

clubs new in the 1970s, absent of graphite. A material ostensibly for

gripping the shaft, but slippery because the designer had a sense of

humor. An intent to make birdies even more difficult.

It wasn’t a birdie I had in mind. Frankly, it was how many strokes

over par the hole would allow me. I was living in hope.

The sun was out, giving shadows to the pine trees preparing for the

chill of autumn. My shorts had pockets to hold the spare ball in

anticipation of losing the one that was sitting on top of the wooden T.

My mum would have been proud of me as a handkerchief was in the

other pocket. A light sweater covered my short-sleeved shirt. I hadn’t

yet seen the need to purchase a skip cap. After all, sun worshipping

was in my genes having had too little of it from living in the west of

Scotland for over 20 years prior to three and a half in New Zealand.

Happily, there were no golfers up ahead. By happily I don’t mean

the threat of my drive hitting them. Rather, I liked being alone, so I

didn’t make a fool of myself with fluffed shots. Even better, there was

no one else behind me as I hated the thought of holding up real golfers

while I searched the woods for my ball.

On that particular day, I knew two things for sure about myself. I

would give my all to get the best score possible even if it meant

navigating through hazards. And the life I wanted to lead had at its

grassroots, a desire to help others.

If I’m honest, there was also a chip on my shoulder from constantly

proving people wrong who had kept telling me what I couldn’t or

shouldn’t do. Thank God some believed in my potential.

In the end, isn’t that what it’s all about, when you stand on the first

tee box? The potential.

I took out my driver. A version that was unforgiving from a bag that

had traveled across the Atlantic with its zip still broken and its head

cover not sure where it belonged.

The left-hand glove had seen better days, but it warranted

inclusion, as did the brand-new ball waiting for its trajectory. I swung

freely to loosen, to prepare, to ask my brain to remind me what should

happen next. All the lessons that had put me in this place on this day.

The BSc honors degree from Glasgow University. The PhD from

Massey in New Zealand. None of it designed to help me play golf. Or

did it?

Education on how to stand and how to swing. Head down, focus on

the ball even if you don’t know where you’re going. Two degrees in

microbiology certainly gave me a focus on tiny organisms.

I swung, hit the ball, and watched it land in the middle of the

fairway, albeit only 150 yards away. A good start on a long journey.

The year was 1982. I had not long received my PhD in Microbiology

from Massey University in New Zealand. The word probiotic wasn’t

part of my vocabulary. In fact, I doubt it was in many dictionaries.

Soon it would become a large part of my life.

This story is not about naming names and reciting history. Rather,

it’s about the whats, whys and wherefores of a field of science long

ridiculed and now providing hope for many.

It’s a personal story with personal opinions. A journey that

began to take shape in my early teens.

My mum was diagnosed with breast cancer. The unbearable news I

received in the middle of studying for school exams that were to decide

my future. The prayers sent out to the universe were as powerful as I

could give. Hoping for a kind reply. The relief was enormous when the

post-surgical prognosis was good. A higher power was listening.

Over forty years later, I published the discovery that there was

potentially a correlation between bacteria in the breast and the risk of

cancer.1 Research that has since been confirmed by others, and that

may one day contribute to preventing that dreaded disease.2-4 The

potential for probiotics to reduce that risk is now a subject of

investigation. More on this later.

During my Glasgow University undergraduate schooling, I spent

some time volunteering in the Royal Alexandria Hospital’s Emergency

Department. Although mostly doing remedial tasks, it was my first

direct exposure to suffering and death. On one occasion, I witnessed a

car accident victim who had so much to live for, losing her life on a

resuscitation bed. A memory that lingered long. And made me ask

myself, and not easily answer, what is a soul?5

My sister took up nursing, a career that would place her at the front

line of care, mostly in emergency situations. Her dedication and daily

challenges influenced my career path. I wanted to pursue research that

benefited people.

All this and an upbringing rooted in Scottish Presbyterian values.

The necessity of grace coddled with the belief that no-one is good

enough for salvation. The latter an albatross around the neck.

Each experience was like a piece of clothing covering me one at a

time, until I was ready to leave the safety nets, and venture on a path to

find how I could fulfill my hopes.

I can’t pinpoint a single moment. Some I will discuss later, but

human suffering, in general, affected me. So much so, I allowed myself

to be open to possibilities.

The first occurred one morning at 8am. In my hand was a letter I

was about to post, accepting a PhD opportunity in Leeds, England.

Except, the mail arrived and presented me with a different

opportunity: to do a PhD in New Zealand. So, I opened the Leeds

letter and rewrote it turning down the position. The chance to see a

country at the other end of the world, especially one that had warmer

weather than Britain, was too much to resist. It felt like I was stepping

closer to my path.

My time in New Zealand turned out to be incredibly memorable for

reasons I won’t explain here. I studied the role of E. coli causing

urinary tract infection (UTI), and that research would plant a seed for

the future. Unfortunately, there was no opportunity to stay in New

Zealand as the normal process for a graduating PhD is to do a postdoctoral

fellowship before being suitable for a faculty position.

And again, fate came into play.

I initially accepted a position in South Africa, the country of my

father’s birth, when three things happened.

The first was an offer to study in Calgary at a lab of a renowned

scientist. I had good memories of a visit to Toronto and of Canada

itself. It seemed a more stable and safer option.

The second was I found out there was a chance I could be called up

to serve in the South African armed forces, even though it would likely

only be as a soldier guarding the capital. I pictured myself standing

guard at some government building and it wasn’t on my bucket list.

The third event was the Falklands War. Although neither Britain

nor Argentina officially declared war, they were close to doing so,

which meant if I returned to Britain, I could get enlisted. As much as I

supported Margaret Thatcher’s troops, I had no desire or sufficient

courage to get seasick traveling the Atlantic then be killed or injured

fighting for that territory.

And so, Canada beckoned.

Within a month of arriving in Calgary, I was sent to Halifax and

Toronto to devise collaborative clinical projects. It was at the latter that

my life path changed dramatically.

I was given the opportunity to join the laboratory of the Head of

Urology, Dr. Andrew Bruce in Toronto, and I took it. Notably, with the

blessing of Dr. Bill Costerton, my Calgary professor. Some of the

students in Calgary still make fun of me as the shortest post-doctoral

fellowship they’d ever seen!

My drive was straight into the unknown. Literally. Driving across

the prairies in a car whose ‘lemon’ engine had just been replaced and

for which I was paying 22% interest. It had an a.m. radio that failed to

find a signal for most of the five-day trip. Plus, there was a snowstorm

one day behind me so I couldn’t stop!

Like my opening analogy, I was driving into a world of unknowns

but optimistic it was the correct move.

As I finally reached Toronto and was stopped at a red traffic light,

an off-duty policeman drove into the back of my expensive lemon! His

breath smelt of alcohol, but I was naïve, didn’t pursue it, got my car

fixed and was keen to turn a different corner.

And so, I headed not into the pond or the trees where fellow PhDs and

university professors kept saying I should go to learn the game and

eventually find the green and the hole. Instead, I was alone on the

fairway.

In fact, one university microbiologist described my choice of working

in a hospital as abandoning science to become a slave to surgeons.

Another said I would never be accepted in traditional university

departments. I wondered if that would actually be a blessing if those

were the kind of people in university departments! Did I mention

wanting to prove people wrong?

At 5’11”, slim, fit with brown hair and a love for modern music,

playing soccer and having fun, Toronto was a wonderful place to be.

An 80s dance paradise.

As I walked the fairway of my life at that time, it was Dr. Bruce

who pointed out the flag. It was his idea nine years before I met him,

that lactobacilli had a role in preventing recurrent UTIs. And so, the

concept of lactobacilli conferring benefits to women’s health was

planted.

I had no idea what lay ahead. As if fog or night was covering the

golf course. It simply felt right. A new laboratory, an enthusiastic

mentor at the heart of patient care, and a novel idea of how to bring

relief from the pain and discomfort of bladder and kidney infections.

Indeed, that suffering often stood right in front of me in the eyes of

patients I came across as they attended offices and clinics. Sitting in

urology rounds listening to residents and senior staff discuss difficult

illnesses, I could envisage the patient’s eyes and their families, just like

the worry I experienced with my mother’s cancer.

Pain and suffering leave indelible marks. Because behind each

patient is a story of unwelcome inheritance.

Of the many women who contacted us in the hope that there were

solutions to their chronic ill health, one provides an example of the

problems they faced.

The woman was from Ohio. She was intelligent, pre-menopausal,

had never born a child, and suffered from so many recurrences of UTI,

it was essentially a constant presence. She had been seen by a plethora

of specialists, from urologists, gynecologists, psychotherapists and

others including one who wanted to remove her uterus and another

who stretched her urethra. She was prescribed antibiotic after

antibiotic, then anti-fungals to treat the yeast infections that followed

the antibiotic treatment.

She tried sitz baths, no baths. Different soaps. No douching.

Nothing worked.

Urine culture results kept coming back as negative or insufficient

to diagnose UTI. Nobody had an answer for her continued

symptomatology.

After scanning the internet for alternative therapies and approaches,

she found a retired microbiologist who tested urine in a different way.

Essentially adding a sample to a set of nutrients and letting any

bacteria that were present grow. This was not a process supported by

mainstream test labs for reasons I will not go into here.

The doctor told her that he found Enterococcus in the urine and

said it was probably the cause of her symptoms. This is a Gram-

positive bacterium known to cause UTI and diagnosed by labs even

when it grows in numbers lower than E. coli.

I will refrain from discussing whether or not this detection process

is reproducible, correct or accurate. For the patient, it provided

satisfaction as it finally identified an organism in her urine that was

known to cause UTI. When she was prescribed antibiotics to treat

Enterococcus, the symptoms improved.

She came to Toronto to learn more about the Lacticaseibacillus

(formerly Lactobacillus but recently reclassified) rhamnosus GR-1 and

Limosilactobacillus (formerly Lactobacillus but recently reclassified)

reuteri RC-14 probiotic strains we were testing, the latter chosen for

inhibiting Enterococcus.

This was the first time I heard about bladder fixation where a

woman can’t get her mind away from the discomfort in her bladder.

Constantly feeling abdominal contraction and needing to pee, knowing

that in doing so, pain awaited.

She was thinking all the time about what to drink; just enough to keep

flushing the bladder but not too much that the washroom visits ruined her

day. Asking herself which fluids made it better or worse. Wanting but

dreading the intimacy with her partner. Whenever possible, looking for

new research, for empathy, for hope. Wondering if there was anything

else she could do. If it was her fault. Trying to think back at how it all

started and where an error had been made that would explain today.

We reassured her it was not her fault. Unlike decades ago, when it

was blamed on poor hygiene, we explained that was nonsense.

The disease was life-changing. It rarely affects men and frankly

I’m not sure how they would cope with it. My gut feeling is they would

have demanded a long time ago that solutions needed to be found to

prevent it and improve its cure rate.

After several visits to the clinic, the woman began using the GR-1

and RC-14 probiotic strains. It would take several weeks, but

eventually she started to feel better. The episodes of urgency and

frequency lessened. Either none or very small counts of Enterococcus

were found in her urine by the microbiologist she consulted.

We knew it could all be a placebo effect. Just the result of empathy

and something new being done to help. If that’s what it was, I came to

think that maybe there is actually nothing wrong with it being a

placebo effect. After all, it was the woman’s well-being we cared

about, and we were not going to suggest our probiotics had now been

proven to work! We weren’t sending out patient testimonials as proof

of efficacy. Nevertheless, her feeling better helped encourage us to

continue.

One thing I did perceive at the time was that too often the medical

system ignored patient mental health issues as a by-product of illness

and was unwilling to try alternatives when the ‘standard’ drug or

surgical treatments failed.

We would like to think the probiotics she used had inhibited the

enterococci, and somehow conferred physiological effects on bladder

contraction, urgency and frequency. The treatment did help the

woman’s own lactobacilli recover after years of being collateral

damage, killed by antibiotics. The fact is, we don’t know if the two

strains played a role, but experiencing her case certainly made me

more determined to understand what happened and why she got better.

To this day, we do not know how UTI occurs nor why. In about

25% cases, it resolves without antibiotics. We also don’t know why in

some women it evokes no symptoms or signs.

There are certainly theories about E. coli ascending from the

rectum along the perineum and into the bladder where it induces

infection. Or ascending from the urethra during intercourse. But this

isn’t foolproof.6

Patients benefit from explanations on why they get sick, but too

often, these are insufficient to remove the anguish and self-blame that

many women feel. Having an empathetic partner can help them realise

it is not their fault.

We need physicians trained to ask about mental wellness and coping

with chronic infection, and who are open to alternative therapies. I won’t

pretend to know the answers, but I have learned enough that answers need

to be found because having no major advance in fifty years is unacceptable.

When the pain and urgent need to pee happen again and again,

despite antibiotic treatment, it’s no wonder a woman’s well-being is

affected. After all, the statistics say that half of the women in the world

will suffer from at least one episode of UTI.

Imagine throughout history how they coped without antibiotics?

The historical data on those who died from these infections have not

been well collected, but one paper revealed that bed rest, narcotic

products and herbal douches were used, presumably until the disease

resolved or killed the patient.7

Today, death can still occur from UTI due to various reasons,

depending on the overall health status and age of the patient and

whether the infection reaches the kidneys and beyond. Despite modern

medical advances, there has not been sufficient effort made to better

manage recurrences of this condition.

In the middle of the fairway, I picked out my 5-wood. Irons stayed in

the bag. I reckoned I could take two more swings and reach the green.

Instead, I whacked the ground, and the ball went a mere twenty yards

towards the trees. That feeling of anger and stupidity was immediate.

The goal of reaching the green in three vanished. This was not going to

be an easy task.

Likewise, working on the lactobacilli that Dr. Bruce had isolated and

believed to be important to prevent UTI, proved challenging. Doctors

stopped us in the hallway joking about yogurt being administered to

the vagina and urethra. ‘Which flavor will you test?’ they’d say,

laughing.

It certainly wasn’t funny to us or the patients.

Applications to research agencies were met with subtle ridicule and

rejection. ‘Why are you doing this when we have antibiotics?’

Thankfully Dr. Bruce had funding to support the research as has

been well-documented and summarised in the scientific literature.8,9

Eventually, it led to the development of two lactobacilli strains for

clinical trials and human use.

Our idea at the time was that in order to prevent E. coli and other

bacteria from causing UTI, we needed lactobacilli to inhibit their

growth on the urogenital skin and entrance to the bladder, and stop

them from entering the urinary tract. This research was done in test

tubes and using cells collected from the urine of women volunteers,

plus some experiments in rats and mice. As will be discussed in

chapter 8, this is not how we would approach such studies today.

By the time I reached the green on this first hole, my shot count was

six. Two putts later I removed the ball from the hole and looked back

along the fairway. The plush green grass, so inviting. The sound of

birds passing their day. Distance traffic, an out-of-sight hum. I marked

my scorecard and headed off to the second Tee shaking my head at how

I’d contrived to shoot a triple bogey.

While I had zero regrets about joining the Toronto lab, the mid-1980s

were filled with research challenges. Try doing something first in a

given field. And see how others react! Look at all the pioneers who

were ridiculed.

It was eighty years since Elie Metchnikoff’s report of attributes

from beneficial bacteria. Why had few others worked on it since?

The response from colleagues, in addition to the one cited above,

can range from excitement to condemnation and even efforts to force

you to abandon your ideas.

The career path that I chose, thankfully still exists today. In fact,

with fewer tenured university positions being offered, more young

scientists are choosing alternative directions. From law to business to

government jobs. Those who find careers in medical settings bear the

hopes of many patients.

With cross-functioning groups being assembled, and gender, race

and indigenous ways becoming more openly considered, the hope is

that breakthroughs can occur in managing UTI and other diseases

across the medical field.

Five years into my position, the things that drove me hadn’t

changed. For all the limitations, mostly mine, I was not about to give

up seeing if this unique concept could actually work.

In the following chapters, rather than repeating scientific reviews

of the probiotic area, I will try to help readers make sense of the

challenges and opportunities that I faced throughout my forty-year

journey. More importantly, I hope to clarify the topic of probiotics that

has become a major part of commerce and everyday life for many

people.

I hope readers will enjoy it, even those who don’t play golf!