Albert Lasker Award
for Special Achievement in Medical Science

Award Presentation by Joseph Goldstein

Victor McKusick is one of my heroes, and I am honored to present him with the Albert Lasker Award for Special Achievement in Medical Science. It is intimidating to attempt to summarize in several minutes the 54-year career of an academic giant like Victor. It may not be possible, but let me try.

Victor was born in 1921 in Parkman, Maine. He has an identical twin brother, Vincent McKusick, who recently retired as Chief Justice of the Supreme Court of Maine. Victor and Vincent were raised on a dairy farm in a tiny town of 500 people. They attended grammar school in a one-room school house. Their high school graduating class had 28 members. Vincent, the first-born twin, was the valedictorian, and Victor was the salutatorian.

It seems uncanny that Victor was born in 1921, a landmark year in the history of genetics. Two of the most influential lectures in genetics were presented within months of Victor's birth. In 1921, Thomas Hunt Morgan presented the Coonian Lecture to the Royal Society of London where he summarized his theory of the chromosomal basis of heredity. Morgan had discovered that genes of the fruit fly are arranged in linear order on chromosomes and that a string of genes can cross from one chromosome to its partner chromosome linked together like beads on a string. These fundamental findings formed the basis of the human gene linkage map that Victor would pioneer 40 years later.

The second 1921 lecture was presented by Hermann J. Muller, at the annual meeting of the AAAS in Toronto. Muller advanced the concept of the gene as the basis of life by virtue of its unique ability to reproduce its own variations. In this lecture, Muller proposed that the newly discovered bacteriophage viruses, like lambda, could be used for genetic research because they also reproduced their variations. Muller made a remarkably prophetic statement, which I quote: "Perhaps we may be able to grind genes in a mortar and cook them in a beaker. Must we geneticists become bacteriologists, physiologists, physiological chemists, and physicists, simultaneously while being zoologists and botanists? Let us hope so." Muller's ideas 76 years ago were way ahead of their time and had little impact on his audience. His colleagues considered him a fanciful daydreamer.

The words and wisdom of Morgan and Muller must have reached baby Victor lying in his bassinet in Parkman, Maine, because Victor followed clearly in their path. He entered the world when the dream of genetics was just beginning to take shape, and his life's work has given reality to that dream.

Like Muller, Victor McKusick is a dreamer. Let me tell you briefly about three of his dreams and how they have been transformed into realities.

Victor's first dream occurred in 1939, at age 18, after reading an article in Time magazine that gave a glowing account of Johns Hopkins Medical School and how it was starting a new Institute for the History of Medicine. Victor had always been a history buff, and this article fired his imagination. He immediately developed a fixation on Hopkins, and after graduation from college, he applied to only one medical school—Hopkins. He arrived in Baltimore on Washington's birthday in 1943, and he never left. Suffice it to say, he has spent 54 years at the same institution. This in itself is a remarkable achievement in academic medicine. Contrast Victor's career with that of another academic giant, Lewis Thomas. After graduating form medical school, Dr. Thomas spent 45 years in 11 different institutions. Clearly, Victor doesn't like to travel.

The second McKusick dream was to make genetics an integral part of clinical medicine. This dream began of all places in the cardiology clinic at Hopkins. In the early 1950s, Victor, who at that time was a card-carrying cardiologist, became fascinated with the Marfan syndrome, an inherited disorder in which affected patients show a bewildering array of telltale signs, such as long arms and legs, spiderlike fingers, dislocation of the lens, and calamitous rupture of the body's main artery. Victor's insight was to recognize that all of these seemingly unrelated findings must be due to the action of a single abnormal gene that disturbs the formation of connective tissue. As he saw more and more patients with other forms of inherited disease, he began to appreciate the importance of Mendelian genetics in sorting out challenging diagnostic medical problems.

In 1957, Victor took over the old syphilis clinic at Hopkins and transformed it into one of the world's first medical genetics units. Today, 40 years later, there are 105 accredited clinical genetics units in North America, with 2000 trainees. Thanks to Victor, medical genetics has been evolved from a backwater academic discipline to one of the most active areas of clinical practice. Not bad for a farm boy from Parkman, Maine!

It's not unreasonable to predict that in 10 years clinical genetics will be the largest and most pervasive of the medical subspecialties. As recently as 1960 there were 6 times more research papers devoted to hernias than to human genetics. Last year, there were only 54 papers on hernias and over 20,000 on human genetics.

Now for Victor's third dream and the wildest of them all. Intrigued by genetic maps of the fruit fly, in the late 1950s Victor began to think seriously about a genetic map for humans. In 1960, he showed that the gene for an enzyme called G6PD was closely linked to the gene for color vision on the X-chromosome. Interesting, but then the X-chromosome is easy to map. After all, it's not too hard to tell the difference between boys and girls. In 1968, Victor did something much more difficult: he mapped the Duffy blood group to chromosome 1. This was a landmark study in genetics. For the first time, a human gene had been localized to one of the 22 autosomes. These exciting findings were presented at the International Congress of Birth Defects in 1969. In his lecture, Victor made an audacious proposal, and I quote: "I propose that detailed exploration of the genetic constitution of man is ripe for an all-out attack. What we should know in full detail are the structure and geography of the chromosomes of man: the full nucleotide sequence of all genes determining the amino acid sequence of proteins and the location of each on the chromosomes of man."

The reaction of the audience to Victor's 1969 talk was as flat as a pancake. Much like the reaction to Muller's lecture in 1921. Colleagues congratulated McKusick for his sense of humor and his fanciful daydreaming. Recall that this was 1969, three years before any of the technical advances in recombinant DNA and gene cloning that would revolutionize molecular biology. Undeterred by the polite, but restrained enthusiasm of the medical genetics community, Victor joined forces with Frank Ruddle at Yale, and together they organized biannual workshops directed at human gene mapping. The first meeting in 1973 attracted only 64 scientists, and only 31 genes were mapped. Today, we know the map location of 4500 genes of known function and 40,000 genes of unknown function. Victor's wildest dream has now become a reality. As the champion of gene mapping, Victor played a crucially influential role, together with Jim Watson, in launching the once controversial Human Genome Project in 1989.

And now for the greatest of Victor's many great achievements the creation: of a reference book indispensable to all human geneticists entitled Mendelian Inheritance in Man. Mendelian Inheritance in Man is a remarkable book that summarizes the facts regarding every human phenotype that has ever been described—over 8,640 at last count. This book could only have been written by a Renaissance figure, a nosologist, and syndromologist with encyclopedic knowledge of clinical medicine and genetics. Mendelian Inheritance in Man is now in its 11th printed edition and is online on the Web. It is affectionately referred to as the "McKusick Bible of Clinical Genetics." I should point out parenthetically that the 11th edition actually looks and feels like a Bible. The pages are tissue-paper thin, and there are two columns of text printed on each page. The rumor is that Victor's latest dream is to have the 12th edition placed alongside the Gideon Bible in every hotel and motel room in the world.

Some of you may have heard about Victor's breeding Burmese cats, raising orchids, and maintaining a bank account in Russia. But I doubt that very many of you know that he is also a connoisseur of neckties. His knowledge of neckties, like that of everything else, is encyclopedic. Ten years ago, Victor and I were together at the NIH for a meeting. I was several minutes late and when I entered the room Victor announced to the Committee that I was wearing a necktie that had been made in Europe. The master diagnostician had spoken, and his diagnosis of a necktie with a European ancestry was correct. Victor then explained to an amazed committee that American neckties have diagonal stripes that run downward from right to left, while European neckties have diagonal stripes that run downward from left to right. But there are two things about neckties that Victor didn't teach me—one is which way the diagonal stripes run on ties made in Japan, and the other is what to say to someone wearing a necktie with horizontal stripes.

Victor, the Lasker Foundation is proud and delighted to present you with the 1997 Special Achievement Award in Medical Science. Your contributions to the field of medical genetics are unsurpassed. More than anyone else, you have educated the medical community on the power of genetics to deal with human diseases, and at the same time you have convinced the scientific community that the human being is just as good a model organism for studying basic genetic mechanisms as are the more traditional models of lambda, E. coli, yeast, roundworms, and fruit flies. You are truly a jewel in the crown of 20th century medicine.