Experiments on Animal Genes Enthuses Longevity Researchers

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“Charles Yogi, 89, a track & field athlete, is part of the Hawaii Lifespan Study.” Source of caption and photo: online version of the WSJ story quoted and cited below.

(p. A18) Based on animal experiments, gerontologists believe that one key to a healthy, longer lifespan may be found in a few master genes that affect cellular responses to famine, drought and other survival stresses. The more active these genes are, the longer an organism seems to survive — at least in the laboratory. Moreover, researchers are convinced that some genes may protect us against the risks of heart disease, diabetes, cancer and dementia.
. . .
Recent insights into the genetics of aging among simple organisms are stoking their enthusiasm. In January, for example, gerontologist Valter Longo at the University of Southern California reported that by altering two genes he made yeast that lived 10 times longer than normal. “We can really reprogram the lifespan of these organisms,” he said. In March, scientists at the University of Washington identified 15 genes regulating lifespan in yeast and worms that resemble genes found in humans. At least three companies are working independently on potential therapies based on the discovery that life span in mammals may be regulated partly by genetically controlled enzymes called sirtuins.

For the full story, see:
ROBERT LEE HOTZ. “Secrets of the ‘Wellderly’; Scientists Hope to Crack the Genetic Code of Those Who Live the Longest.” The Wall Street Journal (Fri., SEPTEMBER 19, 2008): A18.
(Note: ellipsis added.)

Patients “Stuck on Waiting Lists” in Canadian Universal Healthcare

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Source of image: online version of the WSJ article quoted and cited below.

(p. A17) In Ontario, Lindsay McCreith was suffering from headaches and seizures yet faced a four and a half month wait for an MRI scan in January of 2006. Deciding that the wait was untenable, Mr. McCreith did what a lot of Canadians do: He went south, and paid for an MRI scan across the border in Buffalo. The MRI revealed a malignant brain tumor.
Ontario’s government system still refused to provide timely treatment, offering instead a months-long wait for surgery. In the end, Mr. McCreith returned to Buffalo and paid for surgery that may have saved his life. He’s challenging Ontario’s government-run monopoly health-insurance system, claiming it violates the right to life and security of the person guaranteed by the Canadian Charter of Rights and Freedoms.
Shona Holmes, another Ontario court challenger, endured a similarly harrowing struggle. In March of 2005, Ms. Holmes began losing her vision and experienced headaches, anxiety attacks, extreme fatigue and weight gain. Despite an MRI scan showing a brain tumor, Ms. Holmes was told she would have to wait months to see a specialist. In June, her vision deteriorating rapidly, Ms. Holmes went to the Mayo Clinic in Arizona, where she found that immediate surgery was required to prevent permanent vision loss and potentially death. Again, the government system in Ontario required more appointments and more tests along with more wait times. Ms. Holmes returned to the Mayo Clinic and paid for her surgery.
On the other side of the country in Alberta, Bill Murray waited in pain for more than a year to see a specialist for his arthritic hip. The specialist recommended a “Birmingham” hip resurfacing surgery (a state-of-the-art procedure that gives better results than basic hip replacement) as the best medical option. But government bureaucrats determined that Mr. Murray, who was 57, was “too old” to enjoy the benefits of this procedure and said no. In the end, he was also denied the opportunity to pay for the procedure himself in Alberta. He’s heading to court claiming a violation of Charter rights as well.
. . .
Canada’s system comes at the cost of pain and suffering for patients who find themselves stuck on waiting lists with nowhere to go. Americans can only hope that Barack Obama heeds the lessons that can be learned from Canadian hardships.

For the full commentary, see:
NADEEM ESMAIL. “‘Too Old’ for Hip Surgery.” Wall Street Journal (Mon., February 9, 2009): A17.
(Note: ellipsis added.)

Christensen Book Re-Thinks Basic Assumptions About Health Care Innovation

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Source of book image: http://images.barnesandnoble.com/images/34000000/34009038.jpg

Christensen’s new book hit the shelves in December 2008. His ideas on health care are promising, if the special interests don’t get in the way. (I have not yet read the new book, but have read earlier versions of his proposals on how disruptive innovations can improve health care.)

(p. R2) BUSINESS INSIGHT: Your coming book, “The Innovator’s Prescription,” takes a look at health care. How likely do you think it is we’ll see substantial innovation in the structure of the U.S. health-care system?
DR. CHRISTENSEN: Well, one great benefit of the current economic crisis is that it will create pressure to find a real solution to the health-care problem. Right now, emergencies exist at companies like General Motors, which has got to drive the cost of its health care down. Every city and town in America would be bankrupt if they kept their books the way private-sector companies keep their books — because of the obligation cities and towns have taken upon themselves to provide health care for their retirees.
And so we really are in an emergency where it’s likely that employers and health-care providers are open to completely rethinking some of the basic assumptions that made innovation seem impossible. What we’re hoping with this book is that we can just bring a way to frame the problem that can help people reach consensus around a course of action that otherwise, at another time, would have seemed quite counterintuitive.

For the full interview, see:
Martha E. Mangelsdorf, interviewer. “Executive Briefing; How Hard Times Can Drive Innovation.” Wall Street Journal (Mon., DECEMBER 15, 2008): R2.
(Note: ellipses added.)

Leeuwenhoek’s Great Discovery Was at First Rejected by the “Experts”

In the passage quoted below, Hager discusses the reception that Leeuwenhoeck received to his first report of the “animalcules” seen under his microscope:

(p. 42) He hired a local artist to draw what he saw and sent his findings to the greatest scientific body of the day, the Royal Society of London.

(p. 43) Van Leeuwenhoek’s raising of the curtain on a new world was greeted with what might kindly be called a degree of skepticism. Three centuries later a twentieth-century wit wrote a lampoon of what the Royal Society’s secretary might well have responded:

Dear Mr. Anthony van Leeuwenhoek,
Your letter of October 10th has been received here with amusement. Your account of myriad “little animals” seen swimming in rainwater, with the aid of your so-called “microscope,” caused the members of the society considerable merriment when read at our most recent meeting. Your novel descriptions of the sundry anatomies and occupations of these invisible creatures led one member to imagine that your “rainwater” might have contained an ample portion of distilled spirits—imbibed by the investigator. Another member raised a glass of clear water and exclaimed, “Behold, the Africk of Leeuwenhoek.” For myself, I withhold judgement as to the sobriety of your observations and the veracity of your instrument. However, a vote having been taken among the members—accompanied, I regret to inform you, by considerable giggling—it has been decided not to publish your communication in the Proceedings of this esteemed society. However, all here wish your “little animals” health, prodigality and good husbandry by their ingenious “discoverer.”

The satire was not far from the truth. Although very interested in the Dutchman’s discoveries, so many English scientists were doubtful about his reports that van Leeuwenhoek had to enlist an English vicar and several jurists to attest to his findings. Then Hooke himself confirmed them. All doubt was dispelled.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.

A Salute to the Sudanese Medicine Men

One might expect that the Sudanese medicine men mentioned below, might have undermined the British physicians, as potential competition. So either there is more to the story than is sketched below, or else these Sudanese medicine men in 1939 placed the mission of saving lives, above their own narrow short-run self-interest. If it was the later, then they deserve our belated salute.

(p. 236) Meningitis was a vicious disease. The death rate had always been high, and nothing they did had much effect. The British physicians concentrated on nursing the sick and trying to limit the spread of the disease. The only thing different this year came in the form of three small sample bottles of sulfa that had been sent to their clinic for the treatment of strep diseases and pneumonia. Strep diseases were not the problem of the moment in Wau. This meningitis was caused not by strep but by the more common cause, a related germ called meningococcus. Still, they had the new medicine, they had nothing else, and they had nothing to lose. Someone decided to try it on a meningitis patient.
. . .
(p. 237) . . . There were twenty-one patients in the first group. The doctors hoped to save at least a few of them.
A few days later, all but one were still alive. The physicians immediately wired for more sulfa. Once it arrived, one of the British doctors stayed at the hospital while the other two went village to village, administering sulfa to every meningitis patient they could find. They asked the help of local “medicine men,” as they called them, tribal healers whose dispensation was needed before the natives would accept treatment. The Sudanese healers knew how deadly the disease was. They told their people that the physicians had “magic in a bottle.” They told them to take the shots. The physicians traveled day and night, injecting patients in grass huts, under trees, and along roadsides, The results, they wrote, were “spectacular.” Within a few weeks, they treated more than four hundred patients. They saved more than 90 percent of them. They knocked out the epidemic before it could get started.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.
(Note: ellipses added.)

Inability to Patent Sulfa, Delayed Its Marketing

When new uses of old, unpatentable drugs are discovered, there seems to be inadequate incentive to publicize them, and bring them to market. (For example, I think I have seen research suggesting that aspirin and fish oil capsules, are as effective in fighting heart disease as some newer drugs, but are nonoptimally utilized because of perverse incentives.) Maybe a revision of the patent law should be considered that permits some patenting of new uses of old drugs and substances?

(p. 172) It was wonderful that this powerful, inexpensive medicine was now available, but for a year after the Pasteur Institute announcement, no one marketed it seriously in its pure form as a medicine. Because it was not patentable, it was difficult for major chemical or drug firms to see a way to make much of a profit from it. It was not until months after the Pasteur group’s first publication on sulfa that the president of Rhône-Poulenc, an industrial supporter of Fourneau’s laboratory, visited the Pasteur Institute to hear about it. After talking with the researchers he decided to launch Septazine, a variation on pure sulfa that he felt was different enough to allow patenting—and hence profits. Septazine reached the marketplace in May 1936.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.

French Entrepreneur Fourneau Was Against Law, But Used It

The existence and details of patent laws can matter for creating incentives for invention and innovation. The patent laws in Germany and France in the 1930s reduced the incentives for inventing new drugs.

(p. 141) German chemical patents were often small masterpieces of mumbo jumbo. It was a market necessity. Patents in Germany were issued to protect processes used to make a new chemical, not, as in America, the new chemical itself; German law protected the means, not the end.   . . .
. . .
(p. 166) Fourneau decided that if the French were going to compete, the nation’s scientists would either have to discover their own new drugs and get them into production before the Germans could or find ways to make French versions of German compounds before the Germans had earned back their research and production costs—in other words, get French versions of new German drugs into the market before the Germans could lower their prices. French patent laws, like those in Germany, did not protect the final product. “I was always against the French law and I thought it was shocking that one could not patent one’s invention,” Fourneau said, “but the law was what it was, and there was no reasons not to use it.”

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.
(Note: ellipses added.)

Christian Care “Replaced Roman Hygiene with Frequent Prayers and Infrequent Baths”

Hager discusses the medical practices of Paris’ Hôtel Dieu lying-in maternity hospital in the 17th century, that led to widespread, and often fatal, childbed fever:

(p. 114) Every day the senior doctors would arrive on their rounds followed closely by a gaggle of students. They would pull the women’s covers down, pass hands over their abdomens, point, prod, and discuss. Although the physicians’ wigs were carefully powdered, their hands were generally unwashed. Christian care, which emphasized purity of the soul over that of the body, had replaced Roman hygiene with frequent prayers and infrequent baths. In Paris the privies and slaughterhouses (as well as the hospital wards of the Hôtel Dieu) dumped their waste into the Seine, then drew drinking and washing water from the same source. Bedding was washed infrequently. Lice and fleas abounded.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.

Industrialist Duisberg Made Domagk’s Sulfa Discovery Possible

(p. 65) . . . Domagk’s future would be determined not only by his desire to stop disease but also by his own ambition, his family needs, and the plans of a small group of businessmen he had never met. He probably had heard of their leader, however, one of the preeminent figures in German business, a man the London Times would later eulogize as “the greatest industrialist the world has yet had.” His name was Carl Duisberg.

Duisberg was a German version of Thomas Edison, Henry Ford, and John D. Rockefeller rolled into one. He had built an empire of science in Germany, leveraging the discoveries of dozens of chemists he employed into one of the most profitable businesses on earth. He knew how industrial science worked: He was himself a chemist. At least he had been long ago. Now, in the mid-1920s, in the twilight of his years, his fortunes made, his reputation assured, he often walked in his private park alone—still solidly built, with his shaved head and a bristling white mustache, still a commanding presence in his top hat and black overcoat—through acres of forest, fountains, classical statuary, around the pond in his full-scale Japanese garden by the lacquered teahouse, over his steams, and across his lawns.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.
(Note: ellipsis added.)

“Four G’s Needed for Success: Geduld, Geschick, Glück, Geld”

One of Domagk’s predecessors, in goal and method, was Paul Ehrlich, who was a leader in the search for the Zuberkugeln (magic bullet) against disease causing organisms. He systematized the trial and error method, and pursued dyes as promising chemicals that might be modified to attach themselves to the intruders. But he never quite found a magic bullet:

(p. 82) Ehrlich announced to the world that he had found a cure for sleeping sickness. But he spoke too soon. Number 418, also, proved too toxic for general use. He and his chemists resumed the search.

Ehrlich said his method consisted basically of “examining and sweating”—and his coworkers joked that Ehrlich examined while they sweated. There was another motto attributed to Ehrlich’s lab, the list of “Four Gs” needed for success: Geduld, Geschick, Glück, Geld—patience, skill, luck, and money.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.
(Note: do not confuse the “Paul Ehrlich” discussed above, with the modern environmentalist “Paul Ehrlich” who is best known for losing his bet with Julian Simon.)

A True Christmas Story of Hope and Justice

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Gerhard Domagk. Source of photo: http://www.nndb.com/people/744/000128360/

Gerhard Domagk spent most of his adult life in a focused, tireless effort to find the first cure for a bacterial infection. Finally, his laboratory discovered a sulfa drug they called “Prontosil,” that seemed effective against strep and some other infections. Domagk published his first preliminary results on the drug in February 1935 (see Hager, p. 164). An increasing number of doctors began testing the drug on their desperate patients.
Life is not always unfair:

(p. 181) In early December 1935, just after the French published the discovery that pure sulfa was the active ingredient in Prontosil, Domagk’s six-year-old daughter, Hildegarde, suffered a bad accident. She was making a Christmas decoration in their house when she decided that she needed help threading a needle. She was on her way downstairs to find her mother, carrying the needle and thread, when she fell. The needle was driven into her hand blunt end first, breaking off against a carpal bone. She was taken to the local clinic and the needle was surgically removed, but a few days later, her hand started swelling. After the stitches were removed, her temperature rose and kept rising. An abscess formed at the surgical site. She had a wound infection. The staff at the clinic tried opening and draining the abscess. When it became reinfected, they opened it again. Then again. The infection started moving up her arm. “Her general state and the abscess worsened to such a point that we became seriously concerned,” Domagk wrote later. “More surgery was impossible.” She was falling in and out of consciousness. The surgeons were talking about amputating her arm. Once the blood tests showed that the invading germ was strep, Domagk went to his laboratory and pocketed a supply of Prontosil tablets, returned to her hospital room, put the red tablets in her mouth himself, and made certain that she swallowed. Then he waited. A day later her temperature continued to rise. He gave her more tablets. No improvement. On day (p. 182) three he gave her more, a large dose, but there was still no improvement. Her situation was growing desperate, so he pulled out all the stops, on day four giving her more Prontosil tablets, then two large injections of Prontosil soluble. Finally her temperature started to drop. He gave her more tablets. After a week of treatment, her temperature finally returned to normal. The infection had been stopped. By Christmas she was able to celebrate the holidays with her family.

Source:
Hager, Thomas. The Demon under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug. New York: Three Rivers Press, 2007.