Professor Finds Beauty In Violins and Viruses

Mark S. Ptashne is the Renaissance man of Harvard's molecular and cellular biology department.

In addition to being one of the world's foremost molecular biologists, he is also an accomplished violinist, businessperson and art collector.

Ptashne, the Smith professor of molecular biology, says he doesn't know whether his musical talents help him in his scientific research, but he notes that few scientists have such a "peculiar" lifestyle.

"Music goes through my head all the time and that doesn't make me a musician, it's just a fact--it could be that it influences how I write a sentence or think about scientific problems," Ptashne says.

Ptashne demonstrated his skill with the violin at a party he hosted two weeks ago in his Cambridge home to honor Jannic Nusslein-Vol-hard and Eric Wieschaus. The two German researchers will receive this year's Nobel Prize in medicine in December for their research on the development of fruit-fly embryos.

Melvin Chen, a chemistry tutor in Currier House who studied music at the Juilliard School in New York, has practiced the violin several times with Ptashne and accompanied Ptashne in a performance at the party.

"We played a Telemann sonata and some Bartok and the audience was pretty enthusiastic; they liked it," Chen says.

Ptashne says he began playing the violin at age 15 and has improved tremendously in the past decade. Much of the impetus for that improvement has been Ptashne's continual acquisition of better-sounding violins.

"At every stage of my career, whatever money I had plus whatever I could borrow involved a violin," Ptashne says. "It's like houses, you trade up and trade up."

Ptashne says that for much of his life, he has sought a violin capable of producing a peculiarly high-quality sound that has obsessed him for many years.

"I've always had a certain sound in mind and was haunted by that," Ptashne says. "The motivation for what I have done, particularly starting a company, was to afford a better and better violin."

Ptashne says he even tried to convince then-president Derek C. Bok to have the University loan him money to purchase an early Stradivari violin, widely regarded as the best instruments in the world.

Bok did not approve the loan, but undaunted, Ptashne says he sold shares in the violin to friends, which put him "way into debt."

Every July, Ptashne plays at the Yellow Barn Festival, a music festival in Boston sponsored by the New England Music Conservatory. Ptashne says he studies at the Conservatory and tries to practice at least two hours a day.

At the party, Ptashne and Chen played two famous Guarnieri violins which make up part of Ptashne's instrument collection. Chen played the D'Egville, the violin that musician Yehudi Menuhin used to build his career.

"About 10 years ago I got a call from a dealer who said he had the D'Egville," Ptashne says. "I tried the violin and immediately loved it but had very little time to decide."

Ptashne says he decided to make the purchase after consulting Menuhin himself.

"I remembered from Menuhin's biography that he had been associated with this violin so I called Menuhin, and he said it was the greatest violin in the world," Ptashne says. "I sold everything and bought it."

The D'Egville was one of a famous historical pair of twin Guarnieri violins, Ptashne says.

"One of the famous books by the Hill brothers describes [a collector named] Plowden who had these two violins together in 1850," Ptashne says. "A French violin maker named Vuillaume came by and said you will never see two such beautiful Guarnieris," he says. "So they are a famous historical pair that were apart for 100 years."

By an amazing coincidence, Ptashne succeeded in uniting the pair by acquiring the second violin.

"I finally got the violin of my dreams, the Plowden which is another [Guarnieri violin made by] Del Jesu in 1735," Ptashne says. "I was in Sweden giving a lecture and an English dealer and friend of mine called and said that if I flew in to New York City that night I could see the twin of the D'Egville," he says. "I flew there and now they're back together."

Ptashne says he loans his other violins to help young aspiring players.

"I have one violin called a Rocca that's being played by a concert player in New York and I have [another viola] called a Pressenda that's being played in the Borromeo quartet."

Art Enthusiast

In addition to playing the violin. Ptashne is an avid collector of various paintings and sculptures produced by such artists as Matisse, Hoffman and Lachaise.

Ptashne modestly describes his impressive collection of paintings and sculptures as "restricted to things that emotionally move me a lot."

Ptashne says he was particularly moved by the story of 20th-century German painter Hans Hoffman, who taught many prominent modern artists at his Rhode Island school. Although he was a key figure in the modern art movement, Hoffman did not paint many of his well-known pictures until he was 80 years old, Ptashne says.

"[Hoffman's canvases] struck me as being the most moving, unbelievable things," Ptashne says. "As I live with those pictures, they continuously amaze me."

Lambda: More Than a Greek Letter

Despite his profound interest in the arts, Ptashne is still most well-known for his contribution in the field of gene regulation.

As a fellow at Harvard, Ptashne rose to fame after isolating the repressor of lambda phage virus. The lambda virus is able to remain dormant in E. coli bacteria because its repressor binds to the viral DNA, preventing the expression of the genes necessary for viral replication.

The repressor motif is used in gene regulation in many other organisms, but for years, prominent researchers had failed to isolate a repressor, Ptashne says.

"I went into science because I became alerted to the idea of there being a repressor and began collaborating and competing with [Leob University Professor] Wally Gilbert, who was at the time looking for the lac repressor," Ptashne says.

Years later, the ABC television network produced a movie detailing the friendly competition between Ptashne and Gilbert at the recommendation of James L. Watson, co-discoverer of the structure of DNA.

Ptashne recorded his work with lambda repressor in 'A Genetic Switch,' a monograph considered by many scientists to be one of the classics of molecular biology. The book is used by Harvard students taking Biological Sciences 10: "Introductory Molecular Biology," Biological Sciences 14: "Genetics," and Biological Sciences 1: "Introductory Genetics, Molecular, Cellular and Developmental Biology."

After characterizing the lambda repressor, Ptashne began applying the principles of gene regulation in lambda phage virus to higher organisms.

"In 1988 we made a few observations that enabled us to argue that the principles of gene regulation in higher organisms can be understood with certain modifications of what we know in lambda," Ptashne says. "Those principles of gene regulation in higher organisms were then explained in the second edition of 'A Genetic Switch."

Ptashne says he hopes an understanding of the basic mechanism of the repressor's activity can be applied to broader issues, such as determining the evolutionary basis of transcription-based gene regulation.

"[We are studying] how evolution uses a limited number of activators to turn on many different genes in many different programs." Ptashne says. "If you can understand this then you can understand how regulation evolved."

Ptashne is now investigating gene regulation in higher organisms from various angles.

"We are continuing on a variety of fronts using various eukaryotes [such as] yeasts and mammalian cells to understand these chemical principles," Ptashne.

"Our focus is different from that of many labs working on gene regulation." Ptashne says. "It's not so much discovering new examples of regulators but rather understanding what are the common chemical principles that regulate genes. The message from lambda is that you can't study the patterns of gene expression without studying the underlying mechanism."

Ptashne says that Nusslem Volhard's work on the development of front fly embryos shows that many of the complicated patterns of gene regulation during development can be understood in terms of the Lambda mechanism.

"By reiterating these transcriptions elements, you can evidently make a fly," Ptashne says.

A Young Start

Ptashne got his start in research as a high school student working in a neurology lab for a family friend, during which he published two papers on the anti seizual effects of dilantin, a drug commonly used to treat patients with epilepsy.

Faced with the choice between attending Reed or Harvard for college. Ptashne opted for Reed.

"I had the instinct that I wasn't self confident enough to throw myself into a situation which I perceived to be more impersonal," he says.

At Reed. Ptashne says he loved with the idea of medical school and changed his major to philosophy, but ultimately decided to become a scientist after working in a fruit fly genetics lab.

Coming to Harvard as a graduate student in 1961. Ptashne says he was surprised to discover that Reed was more academically rigorous tha Harvard.

"The rigors of Reed in those days were quite extraordinary," Ptashne says "One of the shocking things of coming here was realizing how much easier it was to get through Harvard than Reed."

Principles, Not Pedantics

Ptashne, who now helps teach Bio Sec I, says he stresses concepts in the classroom.

"Students should be able to sit with a small number of pages and see how the whole thing works as a matter of engineering principles," Ptashe says. "You want to grasp the principles because they're not that hard to understand ad once you understand them, they're to easy to forget because they make a coherent whole."

"If students can grasp these fundamental principles then they can grasp the astounding intellectual advances that have been made in the field." Ptashne says. "My problem is to make that narrative vivid."

A Successful-Entrepreneur

Ptashne's success is not continued to the scientific and musical realms he is also a brilliant entrepreneur.

In 1980, Ptashne teamed up with Thomas P. Maniatis, professor of biochemistry and molecular biology to found the Genetics Institute, a local biotechnology company which produces various growth factors and hormones. After serving as a scientific adviser for the company for 11 years, Ptashne left the firm in 1991.

The Genetics Institute now employs over 1,000 people and earned over $1.30 million in revenue last year.

Initially the company was supposed to be a point venture with Harvard. Ptashne says. But Harvard's involvement stirred up controversy, leading former President Bok to withdraw from the project.

"Bok sought me out and asked me if I would start a company with Harvard," Ptashne says "As things got closer to being finalized, Harvard dropped out for a variety of real and managed reasons and form and I continued on

Ptashne says that for much of his life, he has sought a violin capable of producing a peculiarly high-quality sound that has obsessed him for many years.

"I've always had a certain sound in mind and was haunted by that," Ptashne says. "The motivation for what I have done, particularly starting a company, was to afford a better and better violin."

Ptashne says he even tried to convince then-president Derek C. Bok to have the University loan him money to purchase an early Stradivari violin, widely regarded as the best instruments in the world.

Bok did not approve the loan, but undaunted, Ptashne says he sold shares in the violin to friends, which put him "way into debt."

Every July, Ptashne plays at the Yellow Barn Festival, a music festival in Boston sponsored by the New England Music Conservatory. Ptashne says he studies at the Conservatory and tries to practice at least two hours a day.

At the party, Ptashne and Chen played two famous Guarnieri violins which make up part of Ptashne's instrument collection. Chen played the D'Egville, the violin that musician Yehudi Menuhin used to build his career.

"About 10 years ago I got a call from a dealer who said he had the D'Egville," Ptashne says. "I tried the violin and immediately loved it but had very little time to decide."

Ptashne says he decided to make the purchase after consulting Menuhin himself.

"I remembered from Menuhin's biography that he had been associated with this violin so I called Menuhin, and he said it was the greatest violin in the world," Ptashne says. "I sold everything and bought it."

The D'Egville was one of a famous historical pair of twin Guarnieri violins, Ptashne says.

"One of the famous books by the Hill brothers describes [a collector named] Plowden who had these two violins together in 1850," Ptashne says. "A French violin maker named Vuillaume came by and said you will never see two such beautiful Guarnieris," he says. "So they are a famous historical pair that were apart for 100 years."

By an amazing coincidence, Ptashne succeeded in uniting the pair by acquiring the second violin.

"I finally got the violin of my dreams, the Plowden which is another [Guarnieri violin made by] Del Jesu in 1735," Ptashne says. "I was in Sweden giving a lecture and an English dealer and friend of mine called and said that if I flew in to New York City that night I could see the twin of the D'Egville," he says. "I flew there and now they're back together."

Ptashne says he loans his other violins to help young aspiring players.

"I have one violin called a Rocca that's being played by a concert player in New York and I have [another viola] called a Pressenda that's being played in the Borromeo quartet."

Art Enthusiast

In addition to playing the violin. Ptashne is an avid collector of various paintings and sculptures produced by such artists as Matisse, Hoffman and Lachaise.

Ptashne modestly describes his impressive collection of paintings and sculptures as "restricted to things that emotionally move me a lot."

Ptashne says he was particularly moved by the story of 20th-century German painter Hans Hoffman, who taught many prominent modern artists at his Rhode Island school. Although he was a key figure in the modern art movement, Hoffman did not paint many of his well-known pictures until he was 80 years old, Ptashne says.

"[Hoffman's canvases] struck me as being the most moving, unbelievable things," Ptashne says. "As I live with those pictures, they continuously amaze me."

Lambda: More Than a Greek Letter

Despite his profound interest in the arts, Ptashne is still most well-known for his contribution in the field of gene regulation.

As a fellow at Harvard, Ptashne rose to fame after isolating the repressor of lambda phage virus. The lambda virus is able to remain dormant in E. coli bacteria because its repressor binds to the viral DNA, preventing the expression of the genes necessary for viral replication.

The repressor motif is used in gene regulation in many other organisms, but for years, prominent researchers had failed to isolate a repressor, Ptashne says.

"I went into science because I became alerted to the idea of there being a repressor and began collaborating and competing with [Leob University Professor] Wally Gilbert, who was at the time looking for the lac repressor," Ptashne says.

Years later, the ABC television network produced a movie detailing the friendly competition between Ptashne and Gilbert at the recommendation of James L. Watson, co-discoverer of the structure of DNA.

Ptashne recorded his work with lambda repressor in 'A Genetic Switch,' a monograph considered by many scientists to be one of the classics of molecular biology. The book is used by Harvard students taking Biological Sciences 10: "Introductory Molecular Biology," Biological Sciences 14: "Genetics," and Biological Sciences 1: "Introductory Genetics, Molecular, Cellular and Developmental Biology."

After characterizing the lambda repressor, Ptashne began applying the principles of gene regulation in lambda phage virus to higher organisms.

"In 1988 we made a few observations that enabled us to argue that the principles of gene regulation in higher organisms can be understood with certain modifications of what we know in lambda," Ptashne says. "Those principles of gene regulation in higher organisms were then explained in the second edition of 'A Genetic Switch."

Ptashne says he hopes an understanding of the basic mechanism of the repressor's activity can be applied to broader issues, such as determining the evolutionary basis of transcription-based gene regulation.

"[We are studying] how evolution uses a limited number of activators to turn on many different genes in many different programs." Ptashne says. "If you can understand this then you can understand how regulation evolved."

Ptashne is now investigating gene regulation in higher organisms from various angles.

"We are continuing on a variety of fronts using various eukaryotes [such as] yeasts and mammalian cells to understand these chemical principles," Ptashne.

"Our focus is different from that of many labs working on gene regulation." Ptashne says. "It's not so much discovering new examples of regulators but rather understanding what are the common chemical principles that regulate genes. The message from lambda is that you can't study the patterns of gene expression without studying the underlying mechanism."

Ptashne says that Nusslem Volhard's work on the development of front fly embryos shows that many of the complicated patterns of gene regulation during development can be understood in terms of the Lambda mechanism.

"By reiterating these transcriptions elements, you can evidently make a fly," Ptashne says.

A Young Start

Ptashne got his start in research as a high school student working in a neurology lab for a family friend, during which he published two papers on the anti seizual effects of dilantin, a drug commonly used to treat patients with epilepsy.

Faced with the choice between attending Reed or Harvard for college. Ptashne opted for Reed.

"I had the instinct that I wasn't self confident enough to throw myself into a situation which I perceived to be more impersonal," he says.

At Reed. Ptashne says he loved with the idea of medical school and changed his major to philosophy, but ultimately decided to become a scientist after working in a fruit fly genetics lab.

Coming to Harvard as a graduate student in 1961. Ptashne says he was surprised to discover that Reed was more academically rigorous tha Harvard.

"The rigors of Reed in those days were quite extraordinary," Ptashne says "One of the shocking things of coming here was realizing how much easier it was to get through Harvard than Reed."

Principles, Not Pedantics

Ptashne, who now helps teach Bio Sec I, says he stresses concepts in the classroom.

"Students should be able to sit with a small number of pages and see how the whole thing works as a matter of engineering principles," Ptashe says. "You want to grasp the principles because they're not that hard to understand ad once you understand them, they're to easy to forget because they make a coherent whole."

"If students can grasp these fundamental principles then they can grasp the astounding intellectual advances that have been made in the field." Ptashne says. "My problem is to make that narrative vivid."

A Successful-Entrepreneur

Ptashne's success is not continued to the scientific and musical realms he is also a brilliant entrepreneur.

In 1980, Ptashne teamed up with Thomas P. Maniatis, professor of biochemistry and molecular biology to found the Genetics Institute, a local biotechnology company which produces various growth factors and hormones. After serving as a scientific adviser for the company for 11 years, Ptashne left the firm in 1991.

The Genetics Institute now employs over 1,000 people and earned over $1.30 million in revenue last year.

Initially the company was supposed to be a point venture with Harvard. Ptashne says. But Harvard's involvement stirred up controversy, leading former President Bok to withdraw from the project.

"Bok sought me out and asked me if I would start a company with Harvard," Ptashne says "As things got closer to being finalized, Harvard dropped out for a variety of real and managed reasons and form and I continued on