Tag Archives: medical research

2009 Nobel Prize in Physiology or Medicine

This year’s Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

Scientists began to investigate what roles the telomere might play in the cell. Szostak’s group identified yeast cells with mutations that led to a gradual shortening of the telomeres. Such cells grew poorly and eventually stopped dividing. Blackburn and her co-workers made mutations in the RNA of the telomerase and observed similar effects in Tetrahymena. In both cases, this led to premature cellular ageing – senescence. In contrast, functional telomeres instead prevent chromosomal damage and delay cellular senescence. Later on, Greider’s group showed that the senescence of human cells is also delayed by telomerase. Research in this area has been intense and it is now known that the DNA sequence in the telomere attracts proteins that form a protective cap around the fragile ends of the DNA strands.

Many scientists speculated that telomere shortening could be the reason for ageing, not only in the individual cells but also in the organism as a whole. But the ageing process has turned out to be complex and it is now thought to depend on several different factors, the telomere being one of them. Research in this area remains intense.

The 3 awardees are citizens of the USA; two were born elsewhere.
Read more about their research at the Nobel Prize web site.

Molecular biologist Elizabeth Blackburn–one of Time magazine’s 100 “Most Influential People in the World” in 2007–made headlines in 2004 when she was dismissed from the President’s Council on Bioethics after objecting to the council’s call for a moratorium on stem cell research and protesting the suppression of relevant scientific evidence in its final report.

Webcast of Dr. Elizabeth Blackburn speaking at Google:
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Engineer Tried to Save His Sister and Invented a Breakthrough Medical Device

Here is another remarkable example of the great benefit engineers provide society.

How a software engineer tried to save his sister and invented a breakthrough medical device

I wanted to help my sister as much as I could. I went to Medline, where there are hundreds of thousands of documents describing clinical studies, to see what I could find.

There are billions of dollars spent every year on clinical studies. I was surprised to discover that there were sometimes clinical studies of treatments for which there were no clinical applications. The trials would show successful results but no clinical applications.

I found a 1987 Italian funded set of clinical studies that showed successful treatment of tumors by the application of chemotherapy directly into the tumors. But I could find nothing since then.
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It took us two years to do the engineering. And it has taken the FDA seven years and two months to approve the product for sale. We were able to shorten the FDA process a little by saying that it was similar to other devices that had already been approved.

Great stuff.

Merck and Elsevier Publish Phony Peer-Review Journal

Elsevier is one of those publishers fighting open science. They try to claim that the government publishing government funded research in an open way will tarnish science. The argument makes no sense to me. Here is another crazy action on their part: they published a “journal” funded by Merck to promote Merck products. Merck Makes Phony Peer-Review Journal:

Merck cooked up a phony, but real sounding, peer reviewed journal and published favorably looking data for its products in them. Merck paid Elsevier to publish such a tome, which neither appears in MEDLINE or has a website, according to The Scientist.
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What’s sad is that I’m sure many a primary care physician was given literature from Merck that said, “As published in Australasian Journal of Bone and Joint Medicine, Fosamax outperforms all other medications….” Said doctor, or even the average researcher wouldn’t know that the journal is bogus. In fact, knowing that the journal is published by Elsevier gives it credibility!

As I have said the journals fighting open science should have their credibility questioned. They are putting their outdated business model above science. We should not see organizations that are focused on closing science research through deceptive publicity efforts and lobbying efforts as credible.

Nanoparticles With Scorpion Venom Slow Cancer Spread

In a, chlorotoxin molecules, colored blue and green, attach themselves to a central nanoparticle. In b, each nanoprobe offers many chlorotoxin molecules that can simultaneously latch on to many MMP-2s, depicted here in yellow, which are thought to help tumor cells travel through the body. In c, over time nanoprobes draw more and more of the MMP-2 surface proteins into the cell, slowing the tumor’s spread. Image from the University of Washington.

University of Washington researchers found they could cut the spread of cancerous cells by 98 percent, compared to 45 percent for the scorpion venom alone, by combining nanoparticles with a scorpion venom compound already being investigated for treating brain cancer.

For more than a decade scientists have looked at using chlorotoxin, a small peptide isolated from scorpion venom, to target and treat cancer cells. Chlorotoxin binds to a surface protein overexpressed by many types of tumors, including brain cancer. Previous research by Miqin Zhang‘s group combined chlorotoxin with nanometer-scale particles of iron oxide, which fluoresce at that size, for both magnetic resonance and optical imaging.

Chlorotoxin also disrupts the spread of invasive tumors — specifically, it slows cell invasion, the ability of the cancerous cell to penetrate the protective matrix surrounding the cell and travel to a different area of the body to start a new cancer. The MMP-2 on the cell’s surface, which is the binding site for chlorotoxin, is hyperactive in highly invasive tumors such as brain cancer. Researchers believe MMP-2 helps the cancerous cell break through the protective matrix to invade new regions of the body. But when chlorotoxin binds to MMP-2, both get drawn into the cancerous cell.

Research showed that the cells containing nanoparticles plus chlorotoxin were unable to elongate, whereas cells containing only nanoparticles or only chlorotoxin could stretch out. This suggests that the nanoparticle-plus-chlorotoxin disabled the machinery on the cell’s surface that allows cells to change shape, yet another step required for a tumor cell to slip through the body.

So far most cancer research has combined nanoparticles either with chemotherapy that kills cancer cells, or therapy seeking to disrupt the genetic activity of a cancerous cell. This is the first time that nanoparticles have been combined with a therapy that physically stops cancer’s spread.

Full press release

Image of the Common Cold Virus

image created by Dr. Jean-Yves Sgro, Institute for Molecular Virology, University of Wisconsin-Madison, from published X-ray data. larger image

Sequences capture the code of the common cold

Conducted by teams at the University of Maryland School of Medicine, UW-Madison and the J. Craig Venter Institute, the work to sequence and analyze the cold virus genomes lays a foundation for understanding the virus, its evolution and three-dimensional structure and, most importantly, for exposing vulnerabilities that could lead to the first effective cold remedies.

“We’ve had bits and pieces of these things for a long time,” says Ann Palmenberg, of UW-Madison’s Institute for Molecular Virology and the lead author of the new study. “Now, we have the full genome sequences and we can put them into evolutionary perspective.”

As its name implies, the common cold is an inescapable, highly contagious pathogen. Humans are constantly exposed to cold viruses, and each year adults may endure two to four infections, while schoolchildren can catch as many as 10 colds.

“We know a lot about the common cold virus,” Palmenberg explains, “but we didn’t know how their genomes encoded all that information. Now we do, and all kinds of new things are falling out.”
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The newly sequenced viruses also show, says Palmenberg, why it is unlikely we will ever have an effective, all-purpose cold vaccine: The existing reservoir of viruses worldwide is huge and, according to the new study, they have a tendency to swap genetic sequences when cells are infected by more than one virus, a phenomenon that can lead to new virus strains and clinical manifestations.
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The ability of different cold virus strains to swap genes and make entirely new strains was thought to be impossible, notes Claire M. Fraser-Liggett, a co-author of the new study and director of the Institute for Genome Sciences and professor of medicine and microbiology at the University of Maryland School of Medicine. “There is the possibility that this could lead to the emergence of a new rhinovirus strain with fairly dramatic properties,” says Fraser-Liggett.

Value of Prostate Cancer Screening Questioned by Two Studies

Ben Goldacre, in his bad science blog, again takes on journalist’s articles of health research in: Venal, misleading, pathetic, dangerous, stupid, and busted

1410 men would need to be screened to prevent one death. For each death prevented, 48 people would need to be treated: and prostate cancer treatment has a high risk of very serious side effects like impotence and incontinence. These figures are not hard to find: they are in the summary of the research paper.

For complex risk decisions like screening, it has been shown in three separate studies that patients, doctors, and NHS purchasing panels make more rational decisions about treatments and screening programmes when they are given the figures as real numbers, as I did above, instead of percentages. I’m not saying that PSA screening is either good or bad: I am saying that people deserve the figures in the clearest form possible so they can make their own mind up.
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So newspapers ignore one half of the evidence, and they fail to explain the other half properly.
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They can also link directly and transparently to scientific papers, which mainstream media still refuses to do. Journalists insist that we need professionals to mediate and explain science. From today’s story, their self belief seems truly laughable.

He also says some journalists got it right including the Washington Post in, Prostate Cancer Screening May Not Reduce Deaths:

The PSA blood test, which millions of men undergo each year, did not lower the death toll from the disease in the first decade of a U.S. government-funded study involving more than 76,000 men, researchers reported yesterday. The second study, released simultaneously, was a European trial involving more than 162,000 men that did find fewer deaths among those tested. But the reduction was relatively modest and the study showed that the tests resulted in a large number of men undergoing needless, often harmful treatment.

I think it is true that most people need help having science mediated to some extent. But he is also right that those doing so need to do better. And also everyone needs to learn about science to understand the choices they personally and politically (for policy issues) need to make decisions on. Being scientifically illiterate is dangerous.

Scientists Target Bacteria Where They Live

Scientists Learning to Target Bacteria Where They Live

Scientists have learned that bacteria that are vulnerable when floating around as individual cells in what is known as their “planktonic state” are much tougher to combat once they get established in a suitable place — whether the hull of a ship or inside the lungs — and come together in tightly bound biofilms. In that state, they can activate mechanisms like tiny pumps to expel antibiotics, share genes that confer protection against drugs, slow down their metabolism or become dormant, making them harder to kill.

The answer, say researchers, is to find substances that will break up biofilms.
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Melander said “a throwaway sentence in an obscure journal” — the Bulletin of the Chemical Society of Japan — gave them another clue. They isolated a compound from the sponge that disperses biofilms and figured out how to synthesize it quickly and cheaply.
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But dispersing biofilms without understanding all the ramifications could be a “double-edged sword,” Romeo warned, because some bacteria in a biofilm could wreak worse havoc once they disperse.

“Simply inducing biofilm dispersion without understanding exactly how it will impact the bacterium and host could be very dangerous, as it might lead to spread of a more damaging acute infection,” he said.

Monoclonal Antibodies Found That Stop All Flu Types

Universal Flu Drug Stops All Flu Types

A new kind of drug cocktail kills all types of flu bugs and could protect against pandemic or seasonal flu. “I certainly believe that a therapy for all kinds of influenza may be within our grasp,” study researcher Robert Liddington, DPhil, director of infectious diseases at the Burnham Institute in La Jolla, Calif., said at a news conference announcing the finding.

The treatment is based on new monoclonal antibodies that attack flu viruses in a shared Achilles heel. Of the many different subtypes of flu, there are only two basic patterns for this vulnerable, essential part of the flu virus.

And despite heroic efforts, researchers could not breed a flu strain resistant to the treatment — suggesting that there’s only a very small chance that mutated viruses could render the treatment obsolete. The breakthrough finding is a joint effort from labs at the Burnham Institute; Dana-Farber Cancer Institute in Boston; and the CDC in Atlanta.

Like many breakthroughs, the finding was partly accidental. The researchers were, at first, trying only to create a treatment to stop the H5N1 bird flu virus, the most likely candidate for igniting the next worldwide flu pandemic.
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While monoclonal antibodies against flu are new, a wide range of drugs are based on this technology. That means the new, fully human anti-flu antibodies could become new human drugs relatively quickly…

“We hope these antibodies are in clinical trials during the 2011-2012 flu season — maybe earlier,” Marasco said. “This really is an important advance in the field of antiviral therapy. The possibility of having a universal therapy for flu is made more real and possible because of these discoveries.”

Gene Duplication and Evolution

Roughly 10 million years ago, a major genetic change occurred in a common ancestor of gorillas, chimpanzees, and humans. Segments of DNA in its genome began to form duplicate copies at a greater rate than in the past, creating an instability that persists in the genome of modern humans and contributes to diseases like autism and schizophrenia. But that gene duplication also may be responsible for a genetic flexibility that has resulted in some uniquely human characteristics.

“Because of the architecture of the human genome, genetic material is constantly being added and deleted in certain regions,” says Howard Hughes Medical Institute investigator and University of Washington geneticist Evan Eichler, who led the project that uncovered the new findings. “These are really like volcanoes in the genome, blowing out pieces of DNA.”

Eichler and his colleagues focused on the genomes of four different species: macaques, orangutans, chimpanzees, and humans. All are descended from a single ancestral species that lived about 25 million years ago. The line leading to macaques broke off first, so that macaques are the most distantly related to humans in evolutionary terms. Orangutans, chimpanzees, and humans share a common ancestor that lived 12-16 million years ago. Chimps and humans are descended from a common ancestral species that lived about 6 million years ago.

By comparing the DNA sequences of the four species, Eichler and his colleagues identified gene duplications in the lineages leading to these species since they shared a common ancestor. They also were able to estimate when a duplication occurred from the number of species sharing that duplication. For example, a duplication observed in orangutan, chimpanzees, and humans but not in macaques must have occurred sometime after 25 million years ago but before the orangutan lineage branched off.

Eichler’s research team found an especially high rate of duplications in the ancestral species leading to chimps and humans, even though other mutational processes, such as changes in single DNA letters, were slowing down during this period.

MRI That Can See Bacteria, Virus and Proteins

IBM team boosts MRI resolution

The researchers demonstrated this imaging at a resolution 100 million times finer than current MRI. The advance could lead to important medical applications and is powerful enough to see bacteria, viruses and proteins, say the researchers.

The researchers said it offered the ability to study complex 3D structures at the “nano” scale. The step forward was made possible by a technique called magnetic resonance force microscopy (MRFM), which relies on detecting very small magnetic forces.

In addition to its high resolution, MRFM has the further advantage that it is chemically specific, can “see” below surfaces and, unlike electron microscopy, does not destroy delicate biological materials.

Now, the IBM-led team has dramatically boosted the sensitivity of MRFM and combined it with an advanced 3D image reconstruction technique. This allowed them to demonstrate, for the first time, MRI on biological objects at the nanometre scale.

That is very cool.