So researchers in the UK brought in the big guns – bioinformatics.

Cancer Research UK has set up seven British centers to start collecting 9,000 tumor samples from a wide range of cancer patients to create a DNA database. Researchers will extract DNA from these tumors and scan them for a series of key genes involved in tumor development. The results will then be cross-checked against a range of cancer treatments, to create a map of which treatments work best for cancers associated with which particular genes.

This is based on the concept of pharmacogenomics: certain genes predispose people to respond to certain drugs in certain ways. We can already test a cancer patient for a single gene, knowing how tumors with that gene respond to a particular drug. However currently we don’t have a way of testing a broad panel of genes. And to compound the problem, we don’t have a way of quickly and accurately sharing information between labs in the same city, across the country or internationally.

Again, enter the power of bioinformatics.

With the proposed cancer DNA database, a doctor might analyze a patient’s tumor sample and prescribe a tailored treatment plan within a very short period of time, perhaps as little as two weeks.

As Professor Matthew Seymour, director of the National Cancer Research Network (NCRN) in the UK, recently stated, “We have to get clever about how to target drugs. Medications for cancer have to be personalized because no two cancers are identical.”

Bioinformatics research is increasing at an exponential rate. DNA sequences are available to anyone with an Internet connection – along with free bioinformatics tools to explore sequence data, predict the presence of genes, and compare features shared between organisms.

The DNALC has been working in DNA sequencing and bioinformatics for over a decade, developing intuitive, visually appealing computer tools for teachers and students to quickly learn the rudiments of gene analysis and integrate bioinformatics with biochemistry labs.

If you want to find out more, check out:

• G2C Online Bioinformatics section
• DNAi: Applications > Genes and medicine > Genetic profiling
• Gene Boy, a fun, intuitive Flash interface to analyze DNA sequences.
• Sequence Server, a database and personal workspace for students to conduct phylogenetic analyses using their own DNA sequences.
• DNA Subway, a platform that uses the metaphor of a subway network to provide students access to various bioinformatics workflows.

How is it possible that some organisms have the ability to survive in some of the dirtiest places on earth?  What survival mechanisms do they have that differ from ours?

Scientists ground up the brains and other nerve tissues from two species of insects, the American cockroach and the desert locust.  Material extracted from the samples was shown to kill more than 90 percent of a harmful type of E.coli bacteria.  In addition, the tissue extracts killed a type of staph bacteria.  There seem to be nine molecules within the tissue that are involved in defense against microbes.

Although the nine molecules have not been identified, scientists may be able to utilize the molecules in the future as a form of disease prevention in humans.

So that finally puts the autism-vaccination link to bed, right? Wrong. To read some responses in the blogosphere, one could assume that The Lancet had declared war on all humanity. In Natural News, Mike Adams writes that “The Lancet is doing exactly what George Orwell described in 1984 — rewriting history by obliterating scientific truth and removing it from their archives.” In the Age of Autism, Mark Blaxill refers to the General Medical Council’s judgment that precipitated the retraction as “deep and profound censorship”. Now, I have no intention of picking a fight with these people, but what we have here is a failure of logic and some profound cherry-picking of scientific literature. Thus:

1) In 1998, The Lancet publishes a paper suggesting a link between vaccines and autism. The Lancet is right.
2) In 2010, The Lancet retracts the paper. The Lancet is not only be wrong, but corrupt as well.

I want to ask Mr. Adams and Mr. Blaxhill just one question. At what point in the 12 years between publishing an article that confirms your beliefs and the subsequent retraction was The Lancet usurped by Orwellian propagandists?

I suspect the issue here (and I am sure even Mr. Adams and Mr. Blaxhill will agree) is a failure to trust. Some of us choose to trust the medical/pharmaceutical establishments, some don’t. If you don’t have confidence in these institutions, no amount of pronouncements will change your mind. For many, the primary reason to mistrust Big Pharma is that it is profit-motivated. But so are farmers (yes, even organic ones), private hospitals, and the people that make your seat belts. Occasionally they make mistakes and do stupid things but this is not evidence of conspiracy.

If this retraction is a sign of anything, it is of a healthy peer-review process. The Lancet made a judgment, reviewed it, and found it to be in error. It would be great if we were all capable of such logic.

In the emerging field of pharmacogenetics, scientists study genome variations and correlate them with drug treatment response.  For example, variations (also called polymorphisms) in genes encoding enzymes involved in drug metabolism have been found to affect the activation, deactivation, and toxicity of drugs used to treat cancer, heart disease, and psychiatric disorders.  Recently, scientists found that DNA sequence can also be used to predict responsiveness to current Hepatitis C treatment (a 48-week course of peginterferon-α-2b combined with ribavarin).

The sequence at a single DNA position (single nucleotide polymorphism, or SNP) on chromosome 19, close to the gene encoding the interferon-λ-3 protein, has a significant effect on a patient’s ability to clear Hepatitis C infection with treatment.  Patients with a C nucleotide at the critical position on both copies of chromosome 19 (CC genotype) are two to three times more likely to respond to treatment than those patients with the T nucleotide at the same position (TT genotype).

In the case of Hepatitis C, the mechanism by which one sequence is more therapeutic than the other is not yet understood.  However, sequence information can still assist doctors in selecting appropriate treatments: as alternative Hepatitis C treatments become available, doctors may bypass the current treatment for those patients with the TT genotype.

As DNA sequencing becomes cheaper and easier, and genome information becomes elucidated, the personalization of medicine may become a reality.

Carol Greider isolated the Telomeric Gene while at Cold Spring Harbor Lab

What is a Telomere?
A telomere is a region (or cap) of repetitive DNA at the end of every chromosome that basically protects the chromosome from deconstructing. Telomeres are an important element of the cell cycle – after every round of cell division, telomeres get shorter to the point where they no longer exist (and the cell is then destroyed).

What is Telomerase?
Telomerase is an enzyme that works against this type of shortening – it replenishes the chromosome by adding DNA sequence repeats to telomeres regions. It is particularly important during prenatal development, where it buffers against cell-instability and aging. When we mature, telomerase “switches off” in virtually all tissues, ensuring the cell will only complete a certain number of divisions (e.g. 20-70) before dying. The switching off of telomerase is important process in cancer biology – unrestrained dividing (i.e. cell immortality) is a classic hallmark of the cancer cell.

How was the discovery made?

With Joseph Gall, Elizabeth Blackburn pioneered the discovery of telomeres

With a lot of hard work! In 1978, Blackburn and Joseph Gall, then at Yale University, published a landmark paper, identifying telomeres paper as a repetitive chain of six-nucleotide sequences that comprised the chromosomes’ end. In a number of studies in the 1980s Blackburn and Szostak confirmed that these repeats stabilize chromosomes inside of cells and also predicted the existence of the telomerase enzyme.

Blackburn moved to the University of California and recruited Carol Greider as a graduate student. In what the Lasker Foundation described as a “tour de force of biochemistry”, Greider purified the telomerase protein and demonstrated its enzymatic activity. Greider moved to Cold Spring Harbor Laboratory, where she achieved the ultimate milestone of isolating the RNA gene that encodes for the telomeric template.

The award recognizes importance of telomeres and telomerase to understanding the fundamental properties of the cell and cell-division. Telomeres and telomerase are important components of aging and cancer research.

Blackburn, Greider, Szostak, and Gall are currently based in the University of California, San Francisco , Johns Hopkins University School of Medicine, Harvard Medical School, and the Carnegie Institution respectively.

Physiology and Medicine…

The main contenders: Elizabeth Blackburn, Carol Greider, and (possibly) Jack Szostak
The discovery: Telomeres and telomerase
The verdict: Strong favorites

Carol Greider

Blackburn, Greider, and Szostak are well-known in biology circles for discovering telomeres and telomerase. A telomere is a region (or cap) of repetitive DNA at the end of every chromosome that basically protects the chromosome from deconstructing. Telomeres are an important element of the cell cycle – after every round of cell division, telomeres get shorter to the point where they no longer exist (and the cell is then destroyed).

Telomerase is an enzyme that works against this type of shortening – it replenishes the chromosome by adding DNA sequence repeats to telomeres regions. It is particularly important during prenatal development, where it buffers against cell-instability and aging. When we mature, telomerase “switches off” in virtually all tissues, ensuring the cell will only complete a certain number of divisions (e.g. 20-70) before dying. The switching off of telomerase is important process in cancer biology – unrestrained dividing (i.e. cell immortality) is a classic hallmark of the cancer cell.

In 2006, Blackburn, Greider, and Jack Szostak shared a Lasker award for “the prediction and discovery of telomerase”. The Laskers are the US equivalent of the Nobels, and frequently anticipate future Nobel Prize winners. As such, they have to be considered serious contenders for the gold medal.

In 1978, Blackburn and Joseph Gall, then at Yale University, published a landmark paper, identifying telomeres paper as a repetitive chain of six-nucleotide sequences that comprised the chromosomes’ end. In a number of studies in the 1980s Blackburn and Szostak confirmed that these repeats stabilize chromosomes inside of cells and also predicted the existence of the telomerase enzyme.

Blackburn moved to the University of California and recruited Carol Greider as a graduate student. In what the Lasker Foundation described as a “tour de force of biochemistry”, Greider purified the telomerase protein and demonstrated its enzymatic activity. Greider moved to Cold Spring Harbor Laboratory, where she achieved the ultimate milestone of isolating the RNA gene that encodes for the telomeric template.

Nobel Prizes can only be shared by a maximum of three people. If the award is given for the discovery of telomeres and telomerase, then Blackburn and Greider are the strongest candidates. If there is to be a third recipient, then Joseph Gall (Carnegie Institution and Johns Hopkins), who pioneered the original work with Elizabeth Blackburn, might be also be considered a contender. He did not share their Lasker award in 2006, but did win the Special Achievement Award that same year.

Blackburn, Greider, Szostak, and Gall are currently based in the University of California, San Francisco , Johns Hopkins University School of Medicine, Harvard Medical School, and the Carnegie Institution respectively.

The contenders: John Gurdon & Shinya Yamanaka
Their discovery: Nuclear reprogramming (stem cell research)
The verdict: Too soon?

Gurdon and Yamanaka are well-known for their work on stem cells

Gurdon and Yamanaka shared the 2009 Lasker Award for Basic Medical Research for pioneering the process (nuclear reprogramming) for turning adult cells into stem cells. Gurdon rose to prominence in the 1950s observing that nuclei from adult cells, when transferred into eggs, assumed embryonic features. This discovery demonstrated that adult cells retain all their genes and can be re-programmed. In 2006, Shinya Yamanaka achieved this feat, creating pluripotent (undifferentiated) stem cells from adult fibroblasts (connective tissue cells) in mice. In 2007, his team created pluripotent stem cells from human adult fibroblasts. Nuclear reprogramming techniques have significant potential as cancer treatments and many other therapeutic fields.
With the Nobel Prizes, there is typically a significant time lag between the discovery and the award. Yamanaka is odds-on to get an award at some stage but 2009 is probably too soon.

The contenders: James Rothman & Randy Schekman
Their discovery: The mechanisms behind vesicle transport
The verdict: Good contenders

Rothman and Schekman pioneered research into vesicle transport

Again, an uncontroversial choice of two former Lasker Award winners. Rothman and Schekman won the Basic Medical Research Lasker Award in 2002 for discovering the machinery that drive vesicles, the tiny sacs that transport signaling molecules within cells. This process is critical to virtually every physiological function.

Rothman is based in Yale University. Schekman is a biologist at the University of California, Berkeley.

Physics…
Thomson Reuters recently published a list of leading contenders, based on primarily on citations. They include:
Akir Aharonov, Chapman University
Michael Berry, University of Bristol
Juan Ignacio Cirac, Max Planck Institute for Quantum Optics
Peter Zoller, University of Innsbruck
John Pendry, Imperial College of Science and Technology
Sheldon Schultz, University of California San Diego
David R. Smith, Duke University

Check back for our Physics update next week.

Chemistry…

Again, I will defer for now to Thomson Reuters. Potential winners include:

Michael Gratzel, Swiss Federal Institute of Technology
Jacqueline Barton, California Institute of Technology
Bernd Giese, University of Basel
Gary Schuster, Georgia Institute of Technology
Benjamin List, Max Planck Institute for Coal Research

Watch this space!