Feroze Novroji Ghadially, 1920–2014: a personal remembrance

On December 28, 2014, the last of my trio of heroes in the pathology world passed away (1). This one-of-a-kind eccentric genius, so beloved by all who knew him, stood astride the world of ultrastructural pathology during its heyday in the 20th century like a colossus. Feroze Ghadially (Figure 1) was also my friend, and it is to this remarkable man, one of the preeminent pathologists of the 20th century, that I wish to pay tribute to with this personal remembrance.

Figure 1.

Dr. Ghadially at his electron microscope at the University of Saskatchewan, Saskatoon, circa 1980 (age 60).

Dr. Ghadially was acutely aware of his own outstanding abilities and accomplishments and—refreshingly—was not shy about mentioning them. On the other hand, he was able to chuckle at his own idiosyncracies and eccentricities. His disarming ability to laugh at himself is reflected in much of what I write here about his remarkable life and of our friendship of 40 years. This includes direct quotes of some of the funnier things he said during our many telephone chats; they are taken from notes made by me during these conversations.

The enigma that was the brilliant, charismatic Dr. Feroze Ghadially is best understood by first taking a look at the history of his earlier life and career—the years before I first met him. These anecdotes (and some from later years) are from a tongue-in-cheek biography of himself that Dr. Ghadially wrote, in the third person, for a monograph celebrating a decade of Killam Program laureates (2). I have placed the extracts from this biography (actually autobiography) in quotation marks.

A REBELLIOUS YOUNG PRODIGY

“Feroze Novroji Ghadially was born in Bombay, India, of Zoroastrian parents but, for reasons difficult to fathom, his birth was not registered” (3).

“Ghadially's early school days at the St. Xavier's School were traumatic, largely because he refused to accept, without questioning, the printed word, religious dogma, and the rules and regulations which he considered were silly. When virtually daily caning failed to reform this obstinate temperamental rebel, his mother was asked to remove him from school.”

“Before he could get into trouble in the next school (Masters High School), an event occurred which was to transform his life—he encountered the textbook of Physics and Chemistry by Godfrey and Hodges. He still remembers the excitement with which he read and reread the book and tried to do as many experiments as possible at home, including the successful making of gunpowder!”

“Ghadially had exceptional powers of memory and recall which permitted him to memorize and recite entire textbooks as if they were little poems. Now labelled a ‘parrot’ and a ‘freak,’ he made few friends and retreated into the public library where he read innumerable books and magazines, not only on scientific topics but on just about any and every subject imaginable.”

“This large scale extracurricular activity resulted in his failing the matriculation examination of Bombay University in 1935, but he passed his examination in 1936. By this time he had made up his mind to be a scientist, and, when asked at the interview for admission into the premedical course ‘Why do you want to be a doctor?’, he replied: ‘I don't want to be a doctor. I am going to be a medical scientist.’”

Ghadially went on to become a virtuoso violinist (Figure 2) and subsequently took up sculpting in wood, metal, and stone, winning awards for artistic achievement in mosaics and sculpture (Figure 3). In winning prizes in competitions in two consecutive years, he succeeded in bypassing fine arts students and was asked not to participate anymore! (He later told me that he forged his own sculpting chisels and considered sculpting a good exercise in 3D concepts for the morphologist.)

Figure 2.

Dr. Ghadially, an accomplished violinist, at home in Ottawa with his grandchildren, all playing violin, circa 2002 (age 82 years old).

Figure 3.

Dr. Ghadially won many awards for his sculptures (both wood and stone). (a) A wood sculpture created in 1962. (b) “Madonna,” date unknown.

While in premedical and medical school, Ghadially developed expertise in several further fields, including electronics and radio communications, Leica (35 mm) photography (Figure 4), making Newtonian telescopes, and manufacturing and repairing scientific instruments for laboratories. “Little wonder then that Ghadially failed in his final M.S., B.S. examination; ironically, one of the subjects he failed in was Pathology! When he did at last condescend to open Boyd's Textbook of Pathology, he felt the same excitement he had felt when he had opened his first science textbook. He now knew that he was going to be an experimental pathologist.”

Figure 4.

Dr. Ghadially, master photographer, circa 1985 (65 years old).

He moved to England in 1945 and began a long and productive career in this field that resulted in countless scientific papers in peer-reviewed journals, much of this during his tenure at the University of Sheffield. His work included long-term experiments on chemical carcinogenesis and important studies on the histogenesis and biological behavior of cutaneous tumors that included landmark papers on keratoacanthoma. Ghadially has been called the “godfather of experimental keratoacanthoma.”

“Despite the pressure of work at Sheffield University, Ghadially found time to build a greenhouse where he cultivated orchids (Figure 5) and a fish house (Figure 6) where he bred thousands of tropical fish in over a hundred large fish tanks connected by a circulating range system which he had devised. He also served as president of several aquarist societies and traveled widely to lecture on this subject. Further, he authored 54 articles and 4 books on tropical fish which have been reprinted several times.”

Figure 5.

Dr. Ghadially, author of multiple books on flowering plants, holding orchids in his garden in Saskatoon, circa 1990 (70 years old).

Figure 6.

Dr. Ghadially, author of the Advanced Aquarist Guide, among other fish-related books, in front of the 8-foot fish tank he built himself in his home in Sheffield, England, circa 1957 (37 years old).

MARRIAGE

While working on a thesis for his medical degree at St. Thomas's Hospital, London, Dr. Ghadially became romantically involved with Miss Edna May Bryant, responsible for the literature searches, preparing of graphs, charts, and tables, and the typing of the thesis. The couple were married in August 1950. Dr. Ghadially related that “no event has had a greater impact on his work than his marriage, for his indefatigable wife totally banned him from doing any household chores or worrying about money or budgets. On top of this, she has found time to act as his secretary and literary assistant in producing his many papers and books.”

THE DAWN OF HIS PASSION FOR ELECTRON MICROSCOPY

“In 1963 a patient suffering from carcinoma of the breast died and left a substantial sum of money to Sheffield University for cancer research. With the money allocated to the Department of Pathology, an electron microscope was purchased more as a matter of departmental prestige than for any other reason. Nobody, including Ghadially, wanted the instrument or was prepared to spend the time and effort needed to evolve the complex technology associated with electron microscopy. However, when the microscope was installed, Ghadially could not resist playing with it to see what it could do.” The rest, as they say, is history!

PATHOLOGIST IN SASKATOON; OUR FIRST MEETING

“Ghadially came to the University of Saskatchewan in November 1968, with a mandate to develop and direct a laboratory for electron microscopy within the Department of Pathology.” It was there that we first met (Figure 7).

Figure 7.

Dr. Ghadially at his desk at The University of Saskatchewan, Saskatoon, circa 1980 (age 60).

In 1973, the medical school in South Africa where I worked as a young pathologist installed a brand-new Zeiss EM9S2 electron microscope. This quickly led to my becoming hooked on the then-newly emerging field of diagnostic ultrastructural pathology. Thus began a career-long fascination with this discipline. Dr. Ghadially's many papers on ultrastructural pathology became familiar to me from early on.

Fate can play strange tricks: In the course of my efforts in early 1975 to find a job in North America that would allow me and my family to emigrate from South Africa, I placed a job-search advertisement, mentioning my interest in electron microscopy, in an American medical journal. I was delighted to receive a reply from Dr. Ghadially, in Saskatoon, Saskatchewan, Canada, and arranged to pay him a visit later in the year. Thus did my wife, Brenda, and I visit tiny, dusty Saskatoon during our exploratory trip through Canada (4).

He collected us at Saskatoon's King George Hotel which, to our amazement and amusement, he had had difficulty in locating in the half-dozen or so streets that made up this town; immediately after introducing himself, he excitedly telephoned his wife and proudly announced that he had found us! The consummate, endearing “absent-minded professor,” Dr. Ghadially was so focused on his work that he never bothered to develop a sense of direction or pay much attention to travel details. Years later he related two anecdotes that further illustrate this: He once took the wrong flight to New York and on another occasion lost his way to a Greek restaurant and had to return home and start over. It was clear to me from the outset that Dr. Ghadially's passion for his work knew no limits. During this first Saskatoon visit, although graciously inviting me to lunch, he expressed irritation at having to eat, as this took time away from his work!

Dr. Ghadially was in the habit of spending many long hours at his beloved electron microscope. I was amused when he told me that, during the frigid Saskatoon winter months, he would seek relief from the oppressive central heating in the medical school building by escaping to the electron microscope room which, of necessity, needed to be kept at a relatively cool temperature.

Shortly after taking up his post in Saskatoon in 1968, Dr. Ghadially “decided to study a vast variety of normal and pathological tissues and produce a book where just about everything that had ever been seen in the cell with the electron microscope would be catalogued, classified, illustrated, and explained.” Dr. Ghadially continued: “And some 6 years and 40,000 electron micrographs later, his book entitled Ultrastructural Pathology of the Cell was published in 1975.”

During our visit, Dr. Ghadially showed me, in his medical school office, the galley proofs of the first edition of this soon-to-be-published, groundbreaking book, with electron micrographs taken with his Zeiss EM9S2, the very same instrument that I was using in South Africa. Glimpsing this manuscript, I realized that here, in embryo, was a reference work destined to be of inestimable practical value to pathologists all over the world, in both the service and research fields.

Later editions of the book included the matrix as well as the cell itself and eventually required printing as two volumes in order to house all this information (Figure 8). This work has never been equaled, or even imitated, and will doubtless forever remain the ultimate reference on the subject.

Figure 8.

My Ghadially library.

A MENTOR TO ME DURING MY YEARS AT BAYLOR DALLAS (1976–1981)

I purchased the first edition of Ultrastructural Pathology of the Cell while still in South Africa, and it proved invaluable in my early work at our recently purchased electron microscope. It continued to be my mainstay reference when I took up a position at Baylor University Medical Center at Dallas, where I was quickly adopted by Dr. James Martin and his staff in the electron microscopy laboratory. The book was also the main inspiration for a 20-lecture course on diagnostic electron microscopy that I gave the pathology residents at Baylor during my tenure there; this, needless to say, was their first systematic exposure to the subject.

It wasn't long after starting work in the Baylor Electron Microscopy Laboratory that Dr. Ghadially and I began corresponding and exchanging blocks and electron micrographs from interesting or perplexing cases, mainly tumors. We also began an exchange of ideas on cases from Baylor that would eventually lead to the publication of several papers (5).

In 1979, I brought to Dr. Ghadially's attention the emerging diagnostic value of glycocalyceal bodies (and microvillous core rootlets) on which Dr. James Martin and I had been working (6). In 1980, Dr. Ghadially, as a member of the editorial board of the Journal of Submicroscopic Cytology, invited me to write a review on glycocalyceal bodies for this journal. In later years he would refer to this paper (7), which received numerous citations by other authors, as “a classic.”

My interest in electron microscopy also extended to its application in the burgeoning field of nephropathology. Oddly enough, despite being an expert on ultrastructural pathology without peer, Dr. Ghadially had no interest in, or liking for, the ultrastructural aspects of renal disease.

A MENTOR TO ME DURING MY YEARS AT METHODIST (1982–2007); A SECOND VISIT TO SASKATOON

After leaving Baylor at the end of 1981, I joined the new pathologist group formed by Dr. Alex McCracken at Methodist Hospitals of Dallas. I began a long struggle to convince the Methodist administration that the institution needed an electron microscope, especially as it housed a busy nephrology service and a pathology residency program. In 1988 they finally relented, and I promptly enlisted Dr. Ghadially's advice regarding the best instrument to buy. He strongly recommended, “for serious electron microscopy,” the Zeiss EM-10, the same instrument that he himself was using. We thus acquired one of these beautiful instruments, and it gave us outstanding service until its replacement by a digital instrument some 16 years later.

In May 1988, I paid a second visit to Saskatoon which, by then, had blossomed into a bustling metropolis. The electron microscopy division he created in Saskatoon became the “mecca of ultrastructural pathology,” where students from all over the world came to attend his annual tutorials on diagnostic electron microscopy. My visit was not only to attend Dr. Ghadially's course, “Tutorial in Ultrastructural Pathology and Diagnostic Electron Microscopy of Tumours,” but also to reconnect on a personal level with this man who had had such an enormous impact on my professional life. By this time, the Ultrastructural Pathology of the Cell and Matrix had become firmly established as a reference work—“the bible”—and was in its second edition, the third to follow very soon after.

The third edition of Ultrastructural Pathology of the Cell and Matrix, the first to be published as two volumes instead of one, received unusually glowing reviews. Here are extracts from a review written by Dr. P. G. Toner of The Queen's University of Belfast, a superb electron microscopist in his own right:

Every specialty needs its Ghadially, to compile the ultimate work of reference…. It is part of the reviewer's job to criticize. The task is approached in this case with trepidation. Would one complain that Genesis was a bit obscure or the New Testament rather incomplete? … If God had not created Dr Ghadially, Butterworths [the publisher] would certainly have earned our gratitude by inventing him (8).

The tutorial in Saskatoon was, not unexpectedly, most entertaining. Ghadially had a unique and often humorous way of describing his observations. I particularly enjoyed his comment on the pores found in annulate lamellae: These structures, found in the cytoplasm, consist of stacks of membranes that share the morphology of the nuclear envelope in that they contain pores. He described these pores as a “joke created by nature as pores between different parts of the cytoplasm are meaningless!” Dr. Ghadially compared the appearance, seen in tissue culture, of collagen fibers passing right through cells to “kebabs at a barbecue.” And he remarked on the difficulty of discerning detail in “dark cells,” saying that it is “hard to penetrate the gloom.”

This delightful 5-day visit enabled me to gain intriguing insights into Dr. Ghadially's life and philosophy. Around that time, he was being invited to take up a position in Saudi Arabia, in Jedda, which he said sounded to him like a name for a place in outer space. (I imagine he was thinking of the Star Wars Jedi knights.)

He spoke unabashedly about his love for the finer things in life—fine watches and cars and, of course, cameras (at one stage he owned 15 Leica cameras!). He was attracted to gold objects and smoked a pipe with a solid gold bowl and stem. He told me how he set about writing, extolling the virtues of smoking cigars and drinking champagne to help “the ideas flow.” He actually told me that he would take opium if it were legal! He told me that he had once been a classmate of famed conductor Zubin Mehta.

During my visit, Dr. Ghadially talked about his experiences with his book on tropical fish, the Advanced Aquarist Guide (see Figure 8), published in 1969 (9). He received an advance of $500 from the publishers at the time, but no royalties whatsoever, although the book went on to become a bestseller, with sales of 1½ million copies! This little classic, he related, was particularly prone to being stolen from libraries (10). He told me an intriguing story relating to his work on tropical fish: He wrote an article on the white fish parasite, which had devastated the economy of a third-world country that relied on its fishing industry for its subsistence. The method he described of treating the water rescued this small nation's economy from oblivion!

Dr. Ghadially was also very proud of a film he made of kissing fish (a species of tropical fish, the Kissing Gouramis), which was shown on national television and for which he won an amateur film competition.

Dr. Ghadially related how his next major work, on tumor electron microscopy, came to be written: “Around 1977 it became evident that the basic knowledge that had accrued in the field of ultrastructural pathology, thanks to Ghadially and other workers, could be put to practical use in the diagnosis of various diseases, particularly tumours. Because of Ghadially's interest in basic curiosity-oriented research rather than applied research, he was a bit slow to accept this, and adhered to the popular idea of the time that the electron microscope was a research tool and research tool only. When finally the realization dawned, he found once again that two groups of workers, one in the USA and another in Australia, had been working for about a year or two on books dealing with diagnostic electron microscopy. Nevertheless, he joined the race and produced in less than 6 months his book entitled Diagnostic Electron Microscopy of Tumours about 1 year and 2 years before the competition.”

“The first printing of Diagnostic Electron Microscopy of Tumours sold out within 4 months of publication and was listed as one of the top six medical books published in 1983 by the Medical Writers Group of the Society of Authors, London, U.K. A much enlarged (500 pages) second edition of this work was published in 1985” (see Figure 8). Juan Rosai, world-renowned surgical pathologist, stated in his review of the second edition that “it represents a major undertaking by one of the best tumor electron microscopists of the continent and, as such, it will remain a classic in the field” (11). This superbly readable and practically oriented book contained an entire chapter (12) based largely on the work that Dr. James Martin and I published during my years at Baylor.

Dr. Ghadially “was one of the first to embrace the new technique of electron-probe x-ray analysis and he is now considered a pioneer in this field. More papers about electron-probe x-ray analysis of pathological tissues have come out of his laboratory than any other in Canada.”

He published more than one book on joint pathology, the last being Fine Structure of Synovial Joints (13). He sent me an autographed copy as a gift.

In 1984, Ghadially published a slim book on diagnostic ultrastructural pathology intended for use by pathology residents preparing for board examinations (14).

THE LATER YEARS (1989–2014)

In early 1989, after leaving the University of Saskatchewan upon reaching its mandatory retirement age, Dr. Ghadially moved to Ottawa, where he was appointed adjunct professor of pathology at the University of Ottawa. He worked in the pathology department of the Ottawa Civic Hospital and the renowned Canadian Reference Centre for Cancer Pathology on a part-time basis (2 days per week). The difficult-to-diagnose cases referred to the experts who worked there from hospitals all over Canada and abroad provided unique material for his ongoing work on diagnostic ultrastructural markers. During this time, he worked on the fourth and final edition of his magnum opus (15), published in 1997. He dedicated it “To Edna. My wife and grand companion. With unabated love and esteem.” Always looking ahead, he spoke to me 2 years prior to its publication about the possibility of producing a fifth edition, but opined that it would be “gilding the lily.”

Like the late great dermatopathologist, A. Bernard Ackerman, Feroze Ghadially was a master iconoclast and possessed a wonderful gift for explaining the complex and exposing scientific nonsense in the most entertaining way. Because of this attribute, he was (like Dr. Ackerman) a much sought-after speaker at professional meetings. As he himself related in 1990:

Besides being an internationally renowned scientist and scholar, Ghadially is also a popular lecturer who is invited again and again to lecture at universities and meetings all over the world. He is regarded as a charismatic lecturer (orator according to some) who can hold audiences enthralled for hours on end (16).

Nothing epitomizes Dr. Ghadially's skill at mesmerizing his readership as a series of three papers, entitled “As You Like It,” published between 1997 and 2001 (17). Part 3 was to be the last of his more than 200 peer-reviewed scientific papers published over the course of half a century. The publication of these three articles came about as a result of repeated requests “for more” from the many who had attended his talks at meetings of the Society for Ultrastructural Pathology, who had found his incisive comments of practical value.

In the second of this trio of papers, he demolished (among other things) false concepts regarding siderosomes, and hemosiderin vs. ferritin, including the false concept that “tetrads and hexads are signatures of ferritin.” The following extracts from this section give one a feel for Ghadially's particular brand of wit:

There are few topics in pathology so beset with errors and muddled thinking as the one I am about to relate now…. Hard to believe—it stemmed from a focusing artifact and ignorance of the problems of high-resolution electron microscopy! … In summary, then, the so-called signature of ferritin (tetrads and hexads) is a forgery. The improperly focused image of any suitably small electron-dense particle will present as “tetrads and hexads.”

In subsequent papers, Ghadially and coworkers “kept on referring to the contents of siderosomes by the noncommittal term ‘electron-dense iron-containing particles’ and occasionally as ‘hemosiderin particles.’” He commented:

You can imagine the problems we had with reviewers of our papers. They thought we were a singularly backward lot who had not heard about ferritin. We bundled the papers off to other journals where presumably the referees had not heard about ferritin and the papers were accepted! It takes too long to educate referees by post; it is best to make the necessary cosmetic changes and send the paper off to another journal. Be sure to eradicate any sign that the paper has bounced!

His involvement in active pathology practice and his literary endeavors largely behind him, Dr. Ghadially searched for new activities to challenge his ever-active mind. With the same fervor and intensity that he gave to his work in pathology, he began a serious study of investing—the stock market in particular. This activity would come to almost completely fill the vacuum created by his separation from the electron microscope. Without the stock market to occupy his mind, he said, he'd be “bored stupid.” Never intimidated by a daunting challenge, he saw the stock market as a “king-sized brick wall to hit his head against.” Employing his customary thoroughness and energy, he not surprisingly excelled at this activity and “beat the stock market” hollow! In 1993, his investment in seven stocks resulted in a 70% increase in this portion of his portfolio in a mere 6 months and he was named the “top stock picker in Canada”! His love of writing never far from his mind, he eventually contemplated writing a book about different techniques in investing.

Beginning around 1988, Dr. Ghadially would regularly telephone me with investment advice that my wife and I applied, with positive results. He introduced us to “technical analysis,” which proved extremely helpful in growing our portfolio. But by 1999 he confessed that his system of picking stocks wasn't working anymore and complained that one is now “being whipsawed back and forth.” The stock market, he said, was turning into a “nightmare.”

As the 20th century drew to a close, Dr. Ghadially's health began its gradual decline and he began slowing down, no longer seeing specimens but still occasionally lecturing to residents. Prompted, no doubt, by his interaction with residents at that point, he talked about writing a book on normal cellular structure—one “for idiots, or fools,” as he put it, with simple line drawings.

Dr. Ghadially recognized the need for regular physical workouts, but found the gym “boring.” He exercised on a “space-age bicycle” with monitors for the heart rate and the like. But after 10 minutes he “is screaming mad and needs to be sedated!” He preferred to stay fit with the aid of a set of dumbbells that he carried with him all over the world, exercising with them every 20 minutes while he worked.

He complained that he was getting tired of taking pills, the side effects of which were making him more ill than anything else. Saying that “they forget that man is mortal. I'd rather live than just exist,” and that “anything I like is bad for me,” he defiantly continued smoking his pipe and cigars and had all his foods fried—deep-fried!—in butter. “I can't go to bed without an egg on toast.” “Cholesterol must be a very tasty object—all the things that taste nice! Where can I buy some cholesterol? Cholesterol-free? Where is all the cholesterol they removed?!”

I sensed disillusion beginning to creep in: He commented that, in electron microscopy, there is “nothing much going on, no one is interested.” He told me he had found a new interest in the teachings of Buddha and the writings of the Dalai Lama: “If you can't solve a problem, forget it, put it aside, don't cloud your mind. Think only of happy things.”

I shared Dr. Ghadially's dismay at the decline of electron microscopy. In 2002 I wrote to him about my attendance at the United States and Canadian Academy of Pathology meeting in Atlanta the previous year: “There was a half-day session on EM and its future. The meeting was something of a downer, with very few in attendance, and the speakers simply rehashed old ideas and concepts. About the only message I came away with was that EM is alive and well in the pharmaceutical industry.”

However, fascinated, as always, by the progress of technology, Dr. Ghadially expressed his delight at how far digital photography had come and marveled at the fact that, in the “pixel business, the sky is the limit” and that “chips are getting better all the time. It will lick the Leica!” He remarked that computer chips were reaching their limit and that scanning electron microscopes were needed to work on them. If they made the “wires” any smaller, they “won't be there!”

As the years went by, our telephone conversations became fewer, but our emails to each other continued. They were less and less about electron microscopy, and more and more about the many problems besetting the world. Dr. Ghadially bemoaned the existence of “too much government and too many lawyers.” One of his last e-mails consisted mainly of a quote from Shakespeare's Hamlet: “When sorrows come, they come not single spies, but in battalions.”

Then, suddenly and unexpectedly, on the morning of September 15, 2014, I opened an email from Dr. Ghadially and was devastated to read the following sad message. Characteristically, he did not mince his words: “Dear Peter, a few days ago I was diagnosed with having a hepatocellular carcinoma. I should be dead in a month or two. So this is goodbye dear friend. Spread the news to our friends. Your loving friend. Send an email confirming this email.” Thus, on December 28, 2014, Feroze Ghadially passed away at his home. The world that day lost a remarkable citizen and pathologist, and I lost a very dear friend. He was 94 years old.

Dr. Ghadially loved life, his work, and his family with an unmatched intensity and passion. Late in our relationship he remarked to me that he had “never worked in his life,” and that he “does what he likes, when he likes.” I then knew, without a doubt, that the Dr. Ghadially I had known all this time was still—and had always been—the very same brilliant, mischievous child he was all those years ago in India!

Tragically, Dr. Ghadially lost his son, James, a gifted orthopedic surgeon who was 59 years old, to pancreatic cancer in 2012. His wife, Edna, for whom Dr. Ghadially in his last years had provided round-the-clock care at their home during her final illness, passed away shortly after, on February 2, 2015. My heartfelt sympathy to his daughters Ruby (professor of dermatology at the University of California at San Francisco) and Sonia (an information technology consultant) and their families.

Farewell, dear Feroze. It was an honor to be counted among your many friends.