Dr. George Joseph Todaro (born 1937)

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Home  Hall of Fame  Dr. George Todaro

Dr. George Todaro

(1937- , Inducted 2018)

Combining Passions for Science and Racehorses

A world-renowned medical doctor and research scientist, Dr. George Todaro, 81, received his first racehorse (really only a ten percent interest) in 1991 from his wife Dr. Jane Todaro, MD, who is an enthusiastic horsewoman, as a Christmas present. To say that acorn grew into a mighty oak tree could be called an understatement.

According to a press release originating with Islet Sciences Inc. in 2012, “. . . Todaro co-authored the groundbreaking ‘Oncogene Theory’ while at the National Institute of Health (NIH) in 1969, which would serve as one of the foundations of future cancer research. In the early 1990s, as scientific director at Seattle-based PathoGenesis, he developed a treatment that has saved the lives of countless cystic fibrosis patients. His most recent focus is biotechnology, in which he is working to increase the world’s food supply [as CEO of Targeted Growth]. “

The article went on to state that the National Academy of Science member and University of Washington Professor of Pathobiology and department head holds over 20 patents.

Todaro graduated from the New York University School of Medicine Honors Program in 1963.

At age 33, Todaro, along with President Richard Nixon’s press secretary Ronald Ziegler and famed entertainer Elvis Presley, were among the ten chosen by the United States Junior Chamber of Congress (Jaycees) as “Outstanding Men of America in 1970.” (In 1985 the award was updated to the Ten Outstanding Young Americans.)

The busy cancer and biotech researcher had gotten his first exposure to racing while growing up in New York City and had expanded his racetrack adventures to Pimlico and Bowie after moving to Maryland.

That 1991 Christmas present, It May Freeze, would take Todaro to the winner’s circle eight times, though the Florida-bred gelding earned less than $30,000.

Todaro’s first stakes winner came in 1994 when his Washington-bred Acquitted won the Leland Stanford Stakes at Bay Meadows. He also had the second place finisher, Rocky T, in the race for two-year-olds. Both runners were trained by Jerry Hollendorfer.

Todaro’s first runner to make a big impression on the national scene was 1996 Kentucky Oaks (G1) winner Pike Place Dancer. The daughter of Seattle Dancer won a trio of other stakes for the Todaro-Hollendorfer partnership, including a 2 1/2-length tally over the boys in the California Derby (G3). She retired with six wins in eight starts and $578,682 in earnings.

Todaro also experienced the very highs and lows of Thoroughbred ownership with 2013 national two-year-old champion and five-time Grade 1 winner Shared Belief, who was lost from complications to colic in December of 2015.

Among the other top racehorses to carry the Todaro name are: Grade 1 winner and nearly $2.4-million earner Hystericalady, additional Grade 1 winners Lady of Fifty and Sam’s Sister, Grade 2 winners Globalize and Trickey Trevor (the latter who Todaro stands at Allaire Farms in Poulsbo) and Grade 3 winner Bwana Bull.

In the summer of 2009 Todaro joined the partnership racing Dakota Phone, and he was among the joyful party that celebrated the son of Zavata’s head victory (at nearly 38-to-one) over Morning Line in the 2010 Breeders’ Cup Mile (G1) run at Churchill Downs.

This past September, Todaro and partners’ Vasilika, who they had claimed for $40,000 last February, won the $200,000 John C. Mabee Stakes (G2) at Del Mar and then added the $300,000 Rodeo Drive Stakes (G1) at Santa Anita to her record.

One of the original investors in Emerald Downs, Todaro has won several distaff stakes at the Auburn track, starting with Washington champion Gemstone Rush in 2007, and more recently with Rivotella, Kikisoblu and Diamonds R (winner of the 2018 Irish Day Stakes).

When checking through the Equibase owners list (September 2018), Todaro is listed (outside of just himself or with his wife) as a partner in 207 other racing entities! Most include his California-based National Hall of Fame trainer Jerry Hollendorfer or the trainer and his wife Janet’s Hollendorfer LLC. There are also several instances in which fellow physician and Washington Hall of Fame inductee Mark Dedomenico is on board. While there are surely a few duplicates in the mix, Todaro’s influence in racing circles is without question.

https://trainermagazine.com/winners/tag/Dr+George+Todaro

December 14, 2013

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Born in Seattle, Washington, on July 1, 1937, Dr. George Todaro is a professor at the University of Washington who has worked with the National Cancer Institute and National Institute of Health. His research has led to innovations in the treatment of cancer and cystic fibrosis. He is also the founder of several biotechnological companies, including Targeted Growth, a Seattle-based company focused on improving the quality of agricultural products, such as biodiesel fuels.

Todaro’s involvement with Thoroughbreds was literally a gift. For Christmas in 1991, his wife gave him a ten percent interest in a Washington-bred yearling named It May Freeze. Todaro was smitten, so much that became was an investor in Emerald Downs, which opened in Auburn, Washington, in 1996. One of his most successful horses was multiple stakes winner Trickey Trevor, who earned more than $700,000.

Todaro is partners with Hall of Fame trainer Jerry Hollendorfer on Lady of Fifty, who overcame a six-wide trip under Corey Nakatani to win the Grade 1 Clement L. Hirsch Stakes by a length and a half. Most of Todaro’s 70 horses in training are owned in partnership with Hollendorfer. Todaro also has horses with three other trainers and owns several broodmares in California and Kentucky.

1985 (July 22) - via Invivo.PharmaIntelligence.Informa.com , news on "Oncogen"

Saved as PDF : [HX0033][GDrive/  Mentioned : Oncogen Company and Dr. George Joseph Todaro (born 1937)   

 Saved image :  [HX0034][GDrive

Executive Summary : "Bristol-Myers Science and Technology Group VP-Administration Bradley Simmons appointed to new position of president of the Bristol-Myers/Genetic Systems/Syntex cooperative cancer research partnership. [Oncogen Company] will continue under the scientific direction of [Dr. George Joseph Todaro (born 1937)] . . . . "

https://www.pnas.org/doi/abs/10.1073/pnas.69.4.1009

The Viral Oncogene Hypothesis: New Evidence

George J. Todaro and Robert J. HuebnerAuthors Info & Affiliations

April 1, 1972

69 (4) 1009-1015

https://doi.org/10.1073/pnas.69.4.1009

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Vol. 69 | No. 4

Abstract

Recent studies, primarily with mouse, rat, and chicken cells, have provided evidence to support the concept that vertebrates contain the genetic information for producing a type-C RNA tumor virus in an unexpressed form in their somatic cells as well as in their germ cells. This information, which our associates and we postulated has been part of the genetic makeup of vertebrates since early in evolution, can persist for hundreds of generations in cell culture without overt production of virus. It is proposed that the endogenous virogenes (the genes for the production of type-C viruses) and the oncogenes (that portion of the virogene responsible for transforming a normal cell into a tumor cell) are maintained in an unexpressed form by repressors in normal cells. Various agents, including radiation, chemical carcinogens, and, perhaps, exogenously added viruses, may transform cells by “switching on” the endogenous oncogenic information. Some other implications of the viral oncogene theory are presented.


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https://www.asbmb.org/asbmb-today/people/010115/generating-the-3t3-cell-line

Generating the 3T3 cell line, the oncogene hypothesis and horses

By Rajendrani Mukhopadhyay

Jan. 1, 2015 

The NIH 3T3 cell line is one of the mainstays of cell biology, gracing more than 26,000 publications in PubMed. But the only reason the embryonic mouse cell line ever got going, muses George Todaro, was that he was a young student who was willing to head into the laboratory every three days to transfer the cells whether they needed the transfer or not."One would have to be little crazy – or a graduate student," says Todaro with a laugh.

Todaro

The cell line began in the early 1960s as part of a study to understand what properties governed the growth of cells in Petri dishes. Howard Green at New York University had just returned from a yearlong sabbatical at the Pasteur Institute in Paris, where he had learned about cell culture. Green decided to undertake a systematic study of culturing cells to understand better their growth properties. He took on Todaro, who was taking a year off from medical school to work in a research lab, to work with him on the project.

The problem with the existing cell lines at that time was that they"had very dubious history or no history," recalls Todaro. For a fresh start, Todaro and Green isolated fibroblast cells from a mouse embryo of the Swiss-Webster strain. The two researchers separated the cells into a series of Petri dishes and began to play around with conditions to see how they influenced cell growth.

To name the series of plated cells, they went with"3T3,""3T6,""3T12" and so on. The"3" denoted the number of days the cells were allowed to grow on the plates. The"T" stood for"transfer." The number after"T" referred to the hundreds of thousands of cells transferred to a new plate for each passage, as in 300,000 cells, 600,000 cells and 1.2 million cells.

The researchers noted that the cells in 3T6 and 3T12 plates grew over each other and got crowded to the point that they started to resemble tumors. But the 3T3 cells never reached confluence."They were strikingly different in that they were a single monolayer, a nice clean sheet of cells," says Todaro.

Out of all the permutations of cell density and culture conditions that Todaro and Green tried,"3T3 came through as an established cell line," says Todaro."I think the secret was we transferred them every three days whether they needed it or not. As a consequence, they never got confluent." He says that while most people wait for their cells to reach confluency to transfer them into fresh plates, he was willing to head into the lab every three days, whether it was a weekday, weekend or holiday, and do the transfer.

After medical school, Todaro landed a position as a principal investigator at the National Cancer Institute in Bethesda, Maryland. With his students, Todaro says,"I basically made them repeat the 3T3 strategy with NIH Swiss cells," which were cells taken from a different mouse strain.

George Todaro's group at the National Cancer Institute established the NIH 3T3 cell line in 1969.

IMAGE COURTESY OF ATCC 

The new cell line from the NIH Swiss mouse embryo had the same property of being able to grow in flat monolayers, and"it had the further advantage of being highly transfectable by DNA, which the original 3T3 didn’t have," says Todaro. He adds there was a 3T3 cell line from a BALB/c mouse embryo but"the NIH 3T3 became the one of choice, because you could do a lot more genetic manipulations with it."

Along with establishing an important cell line, Todaro made other significant contributions to science. With Robert Huebner, he articulated the oncogene hypothesis in 1969. The hypothesis postulated that the human genome contained the information (oncogenes) that could be usurped by certain viruses to turn normal cells into tumorigenic ones.

For his work with oncogenes, Todaro was selected in 1970 as one of the"Ten Most Promising Men" (Mario Capecchi, who won the Nobel Prize in physiology or medicine in 2007, and Elvis Presley were among the others). This annual award was given by the U.S. Junior Chamber of Commerce to recognize 10 notable young Americans. (The program, better known as the"Jaycees," later became the"Ten Outstanding Young Americans" to include women).

It’s about this point in his career that Todaro expresses regret in hindsight."This whole thing about the oncogene hypothesis – it would have been quite easy for us to have done the experiment that really proved it. We never did that." J. Michael Bishop and Harold Varmus did do the experiment and won the Nobel Prize for it."We should have done it," Todaro says."I thought it was obvious that it was going to work. I do really regret that. We had all the tools."

In the 1980s, Todaro left the NCI for a job at a biotechnology firm called Oncogene and has remained in industry since then. In the 1990s, he and colleagues developed an aerosolized version of an antibiotic called tobramycin. So far, it is the only approved inhaled antibiotic in the United States for treating lung infections – it changed the way cystic fibrosis patients were treated."When I look back on what I’ve done, I probably had more impact on cystic fibrosis treatment than anything else," notes Todaro. These days, Todaro works at a start-up biotechnology company called Targeted Growth to develop transgenic crops with better yields than current ones.

Besides science, Todaro’s other passion is racehorses. He caught the bug while living in Maryland and now is involved in breeding and horse racing. He says he sees similarities between his two passions."You have to make a decision based on incomplete evidence," he says. "But the difference with horse racing is you get a result in a minute and 10 seconds. With science, you go for years and years before you know if you’re following a useful path or if it’s another one of those dead ends."

Indeed, Todaro intertwines his twin passions closely: He named one of his mares Cell Line Forever.


1986 (April 10) - NYTimes : "AIDS RESEARCHERS BEGIN TESTING NEW VERSION OF SMALLPOX VACCINE"

By Harold M. Schmeck Jr.  /   April 10, 1986   /  Source : [HN01RX][GDrive

Mentioned :  Dr. Robert Charles Nowinski (born 1945)  /  Dr. Flossie Wong-Staal (born 1946)  /   Dr. Robert Charles Gallo (born 1937)  /  Dr. George Joseph Todaro (born 1937)  /   Dr. Shiu-Lok Hu (born 1949)   /  Dr. Donald Pinkston Francis (born 1942)  /  Oncogen Company  /  

Scientists have remodeled the most successful of all vaccines and plan to seek approval before the end of the year to test it on humans as a protection against AIDS.

The new vaccine was modified from the vaccinia virus, the only vaccine that has eradicated a human disease, smallpox.

Experts had estimated that the first successful AIDS vaccine would not be developed before the 1990's. If the next stages of the current research are successful, that timetable might be shortened considerably. 

Seeking Federal Approval

Before the drug is tested on humans, approval would have to be obtained from the Food and Drug Administration.

Two research teams successfully used genetic engineering techniques to remodel the vaccinia virus to carry a key gene of the AIDS virus. The gene directs the production of two proteins that act as a disguise, in effect fooling a cell into treating the vaccinia virus like an invading AIDS virus.

Vaccinia virus vaccine, by far the most widely used vaccine ever developed against human disease, has not been used for the general population since smallox was conquered almost a decade ago.

In the new experiments, mice infected with the remodeled vaccinia virus developed antibodies against the AIDS virus. One of the research teams also reported that the virus evokes antibody production in monkeys; their response is likely to be more relevant to the prospects in humans. Value Against AIDS Tested

Neither research group has yet demonstrated that the antibodies protect against infection with AIDS virus. Studies on this point are in progress. Antibodies are best known for their ability to help the immune system protect against virus invasion, and conventional vaccines work by stimulating the body to produce antibodies against an invader.

AIDS is such an unusual disease, however, that protection by antibodies cannot be taken for granted without direct proof. AIDS patients themselves have antibodies against the virus, but evidently get no protection from them. In addition, the AIDS virus is unusually variable in its chemistry. Whether this would affect a vaccine is still unknown.

An advantage of using either the remodeled vaccinia virus or the purified AIDS virus protein is that neither would pose a risk of producing the disease AIDS in the recipient.

In the April 10 issue of Nature, scientists at the National Institutes of Health in Bethesda, Md., and a group from subsidiaries of the Bristol-Myers Company in Seattle reported success in splicing a key gene of the AIDS virus into vaccinia virus.

The gene is the blueprint for two surface proteins of the AIDS virus: one is necessary to the process by which the virus attaches to and invades cells, the other has important structural functions. In the animal tests, cells innoculated with the modified vaccinia virus react as if they had been invaded by an AIDS virus and produce antibodies against it.

Although the two research groups worked independently of one another, they accomplished essentially the same feat. Both remodeled the vaccinia virus and demonstrated that it could be used to produce the AIDS virus proteins in their natural form and evoke antibody production in experimental animals.

'A Critical Step'

''We consider it to be a critical step,'' said [Dr. Robert Charles Nowinski (born 1945)] of the Bristol-Myers group.

He and his colleagues at the drug company's biotechnology subsidiaries in Seattle said they are planning to test the remodeled virus soon to see if it can protect chimpanzees against AIDS virus infection. Their group reported sucessful antibody production in seven of eight monkeys tested.

[Dr. Robert Charles Nowinski (born 1945)] and [Dr. George Joseph Todaro (born 1937)] of the Seattle group said that by the end of this year, they expect to ask the Food and Drug Administration for permission to start safety testing of their experimental vaccine in human volunteers.

Authors of the report from the national institutes are Dr. Sekhar Chakrabarti and Dr. Bernard Moss of the National Institute of Allergy and Infectious Diseases and Dr. Marjorie Robert-Guroff, [Dr. Flossie Wong-Staal (born 1946)] and [Dr. Robert Charles Gallo (born 1937)] of the National Cancer Institute. The institutes are major units of the National Institutes of Health.

[Dr. Shiu-Lok Hu (born 1949)] and Steve G. Kosowski of [Oncogen Company], a Bristol-Myers subsidiary in Seattle and Dr. Joel M. Dalrymple of the Army Medical Research Institute of Infectious Diseases, Frederick, Md.. are the authors of the other report. 

In a telephone interview, Dr. Moss said he favors initial use of the AIDS virus proteins themselves rather than the vaccinia virus as experimental vaccine material. He did not give any timetable for human testing in connection with his group's research.

Dangers Posed by Virus

Dr. Moss, a pioneer in research to remodel the vaccinia virus for uses against other diseases, noted that vaccinia virus could be dangerous to an AIDS patient whose immune defenses were suppressed by the disease.

In some rare cases, vaccinia virus has dangerous, sometimes fatal, side effects, including encephalitis. Many experts have said that taking vaccinia out of retirement would only be justified if the disease in question was, like smallpox, deadly and widespread. Presumably, AIDS could fit those criteria.

A vaccine would not be expected to help patients who already have AIDS. It would be used only to protect people who had not yet been infected with the AIDS virus.

Two Solutions Possible

Dr. Anthony S. Fauci, coordinator of AIDS research at the national institutes and the director of the allergy institute, suggested two possibilities: use of the remodeled vaccinia virus directly as a vaccine or using the virus as a means of producing large quantities of the surface, or envelope, proteins for use as vaccine material.

The remodeled vaccinia virus can be ''an important new tool'' in the study of AIDS and ''may have potential as a vaccine against the disease,'' said an announcement from the institutes.

Live vaccinia virus was the vaccine that totally eradicated the disease smallpox after a worldwide effort that took more than a decade. Smallpox is believed to have been the only major human disease ever to have been eradicated totally by vaccine.

In recent years a few scientific groups, notablly that of Dr. Moss, have been seeking to adapt the vaccinia virus to other uses. The research has shown that the virus can be engineered to protect against the liver disease hepatitis B, against some varieties of herpes virus and other infections as well. None of the research has gone beyond the stage of animal experimentation, however.

Dr. Todaro said many scientists involved in AIDS research have achieved remarkable things within only about three and a half years: discovering the virus that causes the disease, developing diagnostic and screening tests, cloning the virus genes and now finding potential ways of producing a protective vaccine.

Problems With Other Strategies

Many possible strategies for developing a vaccine against AIDS have been considered in recent years, but each has presented serious problems.

In a special article on the subject in the New England Journal of Medicine in December, two experts said the best option may be that of using recombinant DNA techology, known popularly as gene splicing and genetic engineering, to develop substance for use in vaccines.

The authors, [Dr. Donald Pinkston Francis (born 1942)] of the Centers for Disease Control and John C. Petricciani of the Food and Drug Administration noted in particular the possibility of producing proteins or parts of proteins from the AIDS virus. A problem with this approach, they said, is that the vaccine recipient's body might not react against these substances in quite the way they would react to the virus itself.

Other experts noted that the vaccinia virus approach also has problems, including the risk of serious adverse reaction if the vaccine is given inadvertently to a person already compromised by the disease.

1986 (Sep 25) - NYTimes : "ANIMALS RESPOND TO EXPERIMENTAL AIDS VACCINE"

By Harold M. Schmeck Jr.  /  September 25, 1986, Section A, Page 20  /   Saved source : [HN02AJ][GDrive

Mentioned :   Genetic Systems Corporation   /   Dr. George Joseph Todaro (born 1937)   /  Dr. Shiu-Lok Hu (born 1949)  /  Oncogen Company   

An experimental vaccine against the AIDS virus produces two important kinds of immune reaction in animals, according to a new research report.

The study, reported in the Sept. 25 issue of Nature by a research team in Seattle, involved the use of vaccinia viruses that were genetically altered to contain key proteins of the virus that causes acquired immune deficiency syndrome. In effect, the AIDS proteins disguise the vaccinia virus so that the body thinks it has been invaded by AIDS virus.

In the experiments, the animals showed evidence of developing the two major types of immunity that are crucial to the body's defense against virus invasion: protective antibodies and cellular immunity. Cell-mediated immunity is dependent on the action of defensive white blood cells, particularly T cells and their products.

The evidence that both were produced in the experiments indicates that the research is advancing toward the goal of developing a vaccine to protect against AIDS, experts said. But there would still be a need for proof that such an experimental vaccine actually protected against the virus under natural circumstances of infection. Because of the complexity of AIDS as a disease, this point cannot be taken for granted. A Key Step in Research

''We believe this is the first report demonstrating T-cell mediated immunity to the virus that causes AIDS,'' said the new report, by scientists of two biotechnology companies in Seattle, [Oncogen Company] and [Genetic Systems Corporation], and the University of Washington. The companies are subsidiaries of the Bristol-Myers Company. The authors of the report are Joyce M. Zarling, William Morton, Patricia A. Moran, Jan McClure, Steven G. Kosowski and [Dr. Shiu-Lok Hu (born 1949)].  

Earlier this year, the scientists reported antibody production against the AIDS virus in animals given the experimental vaccine, but the other type of response was not demonstrated. Other research teams have also reported antibody production in animals that were immunized either with genetically engineered vaccinia viruses, pure substances derived from the AIDS virus or synthetic chemicals that mimic part of the virus.

The most familiar response produced by immunization against a virus is the production of protective antibodies that help eliminate the virus from the body. But cell-mediated immunity, governed by immune defense cells, particularly the T-cells and their products, is also crucial to the body's defense. Some T-cells contribute to antibody production, but others kill cells in the body that are already infected with a virus. This selective cell-killing helps prevent the infection from spreading.

In the new report, macaque monkeys were given the genetically engineered experimental vaccine. Later, samples of their blood were exposed to purified AIDS virus.

The animals developed antibodies against the virus and also produced activated T cells that proliferated and produced an important defensive substance, interleukin-2. Eight monkeys that were given booster doses of the vaccine produced high levels of antibodies, activated T cells and interleukin 2.

In a a late addition to their paper, the scientists said chimpanzees were also tested with the remodeled vaccinia virus and that the animals produced both the helper T cells that aid in antibody production and cytotoxic T cells that can actually kill infected cells.

Findings Termed Impressive

Dr. Bernard Moss of the National Institute of Allergy and Infectious Diseases, a world leader in research in modifying vaccinia virus for vaccine purposes, said he considered the new experimental results ''important and impressive.'' His group has also modified the vaccinia virus to make it evoke antibody production against the AIDS virus.

[Dr. George Joseph Todaro (born 1937)], scientific director of [Oncogen Company], noted that AIDS patients often had antibodies against the AIDS virus, but were not protected against the fatal infection. He speculated that they might lack the cellular immune reaction that has been produced in the experiments with monkeys and chimpanzees.

Vaccinia virus is the active substance of smallpox vaccine, the most successful vaccine ever developed. It was used in a massive global public health effort that eradicated smallpox from the world.

In recent years, several scientific teams including Dr. Moss's at the National Institutes of Health and the group on the West Coast, have sought to modify the vaccinia virus for use against other infections. But the vaccinia virus is potentially hazardous to some people. For that reason, some experts doubt that it will be brought into use again for anything but a widespread deadly disease.

AIDS fits this criterion, but how soon a vaccinia-based vaccine against AIDS might be tested in humans is unclear. Any AIDS vaccine project would first have to solve many serious scientific, social and logistical problems.

Earlier this year, Dr. Todaro's group said they hoped to ask the Food and Drug Administration for approval by the end of this year for initial tests of an experimental vaccine in humans. Yesterday he said they still hoped to do so.

1988 (Oct 01) - NYTimes : "Patents; Snake Venom Is Said To Curb Some Cancers"

By Edmund Andrews  /   October 1, 1988, Section 1, Page 36  /   Saved source : [HN02AK][GDrive]  

Venom from the Western diamondback rattlesnake may prove useful in the war on cancer.

Oncogen, the biotechnology subsidiary of the Bristol-Myers Company, has isolated one of the venom's active poisons, and found that it stops the growth of breast, colon and lung cancer cells.

''We recognize that snake venom might be the source of some very powerful molecules, and we decided to go about purifying it and find out what the active principal was,'' said Dr. George Todaro, president of Oncogen and one of the researchers who made the discovery. The key ingredient, he said, is a fairly simple amino acid that can easily be duplicated.

The researchers are now trying to bind that poison to a genetically engineered antibody that selects particular cancer cells as a target and can deliver the poison to sites where it is needed.