Telomeres, Telomerase and The Graduate Student

By Amy Price PhD
Carol Greider was still a graduate student when she started work on a project that along with Elizabeth Blackburn and Jack Szostak  won this year's Nobel prize for medicine. These US-based researchers  discovered how the body protects the chromosomes housing vital genetic code.

Genetics intrigue me because they are beautifully ordered and I have wondered and asked how the telomeres and telemorase are sequenced. When the telemeres are shortened life span is reduced whereas if there is uncontrolled growth cell corruption occurs. These scientists did more than ask they worked together to find answers.

Elizabeth Blackburn, of the University of California, San Francisco, and Jack Szostak, of Harvard Medical School, discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation.


Joined by Johns Hopkins University's Carol Greider, then a graduate student, Blackburn started to investigate how the teleomeres themselves were made and the pair went on to discover telomerase - the enzyme that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion.

Some inherited diseases are now known to be caused by telomerase defects, including certain forms of anaemia in which there is insufficient cell divisions in the stem cells of the bone marrow. Apparently elevated telomerase can be a biological marker for malignancy and there is research underway to see if vaccines can be developed to arrest the defects.

The Nobel Assembly at Sweden's Karolinska Institute, which awarded the prize, said: "The discoveries... have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies."

Disease and Genomic Advances

By Amy Price PhD

Until recently only a geneticist Francis Crick and one other individual have had their genome read. Apparently Dr Crick did not wish to know if he had a specific dominant gene for dementia but was happy to know all other variants. No one knows the public impact in the face of fullscale  genetic information and there are ethical concerns as genetic engineering has not enjoyed a widespread safety or success rate but it appears the tide may be shifting.

A 5 month old male baby from Turkey was critically ill. Scientists and doctors teamed together from multiple nations to enable the reading of  his genome quickly and were able to work out that he had a wrong diagnosis. This was reported in 'Proceedings of the National Academy of Sciences'. The analysis only took ten days and determined that the boy suffered a genetic mutation that coded for a gut disease that eventually destroys other organs including the kidneys. Additional clinical tests determined that the boy had the rare disease and he is now recovering.

The boy's physician sent a blood sample and Dr Lifton of Yale Medical school along with teams in Beirut and Turkey decoded the DNA to reveal a diagnosis. The scientists did a follow up study with 39 patients who had the same condition the boy was originally thought to have and found that five them had the same genetic mutation. For practical reasons, the initial concentration is on the small percentage of the genome which codes for proteins rather than the non coding DNA.

Rather than the usual method of  looking one gene at a time hoping to guess which was the right gene causing the problems,  a new method was utilized where they could look at all the genes in the genome simultaneously.  They identified a specific allele which had mutations on both copies and which causes the sufferers not to be able to absorb water or electrolytes through the gastrointestinal tract.

This is a turning point in personalized predictive medicine. Professor Mike McCarthy, a geneticist at Oxford University commented, "This is an interesting study - lots of groups are now using the power of new methods for sequencing the human genome to find DNA changes that underlie rare diseases (and increasingly for common diseases too)".

There is tremendous potential for Genomics to pave the way for diagnostic breakthroughs.

Predictive Medicine

By Amy Price PhD

Predictive medicine can change our tomorrows today. Regenerative medicine can replace artificial body parts with lab grown technologies while genetic breakthroughs can save families from generations of genetic disability. It is possible that new knowledge of human genetics and cell biology is likely to transform medical practice. Three likely scenarios could evolve:

•Genetics will lead to the classification of diseases on the basis of the underlying genetics or biochemistry, rather than by symptoms alone leading to preventive rather than crisis orientated treatments.
•Genetic information will identify people who are likely to respond to drugs, or to be harmed by them (pharmacogenetics). This is already possible with certain psychotropic drugs on an experimental level but has not trickled down into mainstream medicine.
•Genetic variation will be a new ‘susceptibility factor’, permitting monitoring and early treatment or, perhaps prevention, of an increasing proportion of common, multifactorial diseases, such as coronary heart disease, hypertension, stroke, cancer, diabetes and Alzheimer's disease. Even stress management can be amplified with knowledge of individual genotypes

It is the genetic variation susceptibility factor which is considered to be the change maker for the advent of predictive medicine. This could lead to regenerative medicine on a cellular (somatic) level or even in vitro gene manipulation (germ line therapy) which could prevent intergenerational transfer of genetic disabilities.
Predictive medicine, when it comes, will be based on a much wider use of genetic testing, at present the gap between what the healthcare system is geared up and trained to deliver and what is scientifically viable is huge. For example there are treatments approved for traumatic brain injury that are effective but most be given within a couple of hours of trauma. This can’t happen now because emergency room personnel are not adequately trained or equipped to diagnose MTBI... As with any new technology applied to health in the context of a complex delivery system, implementation is not going to be simple.

First, of course, there needs to be demand from medical personnel and the general public. Typically wide spread change will only take place after the following criteria are established:

•Demonstration of clinical effectiveness and patient safety – through statistically valid clinical trials
•Cost-effective for general use – through economic analysis of trials and other data;
•Standardization of technology, and quality control – generally through outside regulation of suppliers and laboratories;
•Allocation of resources;
•Recruitment and education and training (or retraining) for health workers – including specialists, MDs, nurses, counselors and technicians. For instance a surgeon who makes a good living performing spinal fusions and cervical repairs will need significant convincing, retraining and motivation to become an early adopter of treatment that makes the previous way of doing business obsolete.

Predictive, regenerative medicine may be the wave of the future. History teaches us that the way to greatness is to find a way to serve many. My dream is to witness a generation of scientists and medical professionals join in unity with a foundation of integrity to build a tomorrow for the patients and public who have make their careers possible.

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Materials adapted from Open University Course Materials (accessed july,2009)