Bangalore, Dec 1, 2007:  Year 2007 can easily be classified as the turning point for the life sciences industry. It saw the completion of the second phase of HapMap Project—created to identify and catalog genetic similarities and differences among populations around the world. Scientists from six countries worked on it. The first phase, completed in 2005, provided data that has led to the development of techniques used in the search for genes associated with common diseases. It has also helped in the identification of 50 such disease-associated genes.

However, the biggest feat is the “designer genome” brought into existence by famed scientist Dr Craig Venter. Using lab-made chemicals, Dr Venter’s team stitched together a chromosome that is 381 genes long and contains 580,000 base pairs of genetic code. This has made artificial life a not-so-distant possibility.

Worldwide there were a number of breakthroughs ranging across segments of pharma, biotech and medical technology and a good measure of work happened in APAC countries. While Australian drug discovery company Phylogica focused on finding new Phylomer drugs, the Japanese scientists developed molecular scissors that open and close in response to light and make for a great invention with applications in manipulating genes and other molecules. In Malaysia, scientists developed herbal drug for dengue and scientists in Thailand discovered oral AIDS vaccine while Indian life sciences industry saw the launch of a number of vaccines.

In the ensuing pages BioSpectrum brings to you a recap of some of the breakthroughs, technologies, products and people who made news in 2007.

Breakthroughs Round up 2007
Drug-resistant TB genome sequenced, a small win
A breakthrough that will help fight the deadly disease of tuberculosis has been achieved in South Africa. The genome of one strain of an extensively drug-resistant tuberculosis (XDR-TB) has been sequenced there, using technology developed in the United States.

“We consider this a breakthrough because it will provide for more analysis of MDR (multi drug-resistant TB) and XDR-TB (extensively drug-resistant TB), and to understand the differences between them,” said Dr Carl Montague of LifeLab, a biotechnology project funded by the South African government.

Elsewhere in the world, researchers are on way to develop two highly potent shorter-term tuberculosis drugs. Two anti-TB drugs (Moxifloxacin and PA-824) have reached the advanced stages of clinical trial and could be available worldwide by 2012-2014, raising hopes for shorter-duration treatment and fighting the bacterium that has become immune to the present drugs.

Developed by TB Alliance, Moxifloxacin has reached the phase III stage of clinical trial and 900 patients were given the drug in the three phase II studies conducted on it. While the second drug, PA-824, has entered the phase II trials and will be now given to TB patients to study its short-
term potency.

Designer genome, a big feat
A team of 20 top scientists put together by Dr Craig Venter has been successful in constructing a synthetic chromosome, a feat of bio-engineering. Using lab-made chemicals, they have stitched together a chromosome that is 381 genes long and contains 580,000 base pairs of genetic code.

This makes creation of artificial life form possible.

The DNA sequence is based on the bacterium Mycoplasma genitalium which the team pared down to the bare essentials needed to support life, removing a fifth of its genetic make-up. The team of scientists successfully transplanted the genome of one type of bacterium into the cell of another, effectively changing the cell’s species.

The new life form depends on the molecular machinery of the cell into which it has been injected for its ability to replicate and metabolise, and in that sense it will not be a wholly synthetic life form. However, its DNA is artificial.

Regenerative medicine —newts show the way
Regenerative medicine went a step further with scientists discovering a key protein that helps newts regrow severed limbs.

Ability of newts and salamanders to renew damaged body parts has been the trigger for this research that holds the promise of limb regeneration in mammals. A British research team found that a protein nAG, secreted by nerve and skin cells, plays a central role in producing a clump of immature cells, known as a blastema, which regrows the missing part.

The importance of nAG was demonstrated by the fact that even when a nerve was severed below the stump tip, which would normally prevent regrowth, the scientists were able to coax regeneration by artificially making cells produce the protein, reported news agency Reuters.

The focus now is on applying the finding in a mammalian context.

Biochip for cancer diagnostics
A new biochip technology has been developed by scientists at Taiwan’s Academia Sinica which likely have important implications in cancer diagnostics. Using a so-called ‘glycan tagging system’, the method allows for the monitoring of cell surfaces and intracellular trafficking of glycoproteins.

It is known that more than 80 percent of human proteins have sugars attached, called glycoproteins. The process of protein glycosylation is known to play a central role in mediating protein function in living organisms. It is also known that altered glycosylation is often associated with inflammation and cancer metastasis. Therefore, the detailed correlation between glycosylation and biological or pathological status is of great interest and may provide information for disease diagnosis and treatment. According to the researchers, their new biochip technology can monitor this correlation and so will be useful for isolating and identifying the glycoproteins that are expressed differentially under various physiological or pathological conditions.

Phylomers identify drug candidates
To find new Phylomer drug candidates, Australian drug discovery company Phylogica is searching the world’s most diverse library of protein shapes which is derived from ancient bacteria, called archaebacteria, that have evolved over millions of years.

Phylogica has patented this technology and is ‘mining’ this biological resource intensively as it turns out to be very rich in active peptide drug candidates. According to reports it is the first company to look at the importance of the shape within such proteins as a source of drug leads, independent of their original function. Phylogica has positive data from Phylomers developed for stroke and burns treatments and is developing other Phylomer candidates for inflammatory diseases such as diabetes and rheumatoid arthritis.

RNAi for crop protection
Scientists working at Monsanto and Devgen have identified a new technology to protect crops from insects.

The technology is expected to provide farmers with a new in-the-seed option to protect crop yields and present another tool to support agriculture’s mission of meeting the world’s growing food, feed and fuel demands.

The technology, called as RNA interference or RNAi, is a biological mechanism found in nature as a way to regulate gene expression. The scientists at Monsanto identified novel applications of RNAi, enabling plants to be better protected against insect pests that feed on crops and impact yield.

Products Round up 2007
A digital insulin pen with memory

Eli Lilly & Company simplified the daily management of diabetes by launching the first insulin pen with memory, HumaPen MEMOIR.

MEMOIR is designed to meet the needs of people with diabetes who take several shots of mealtime insulin each day. It presents sophisticated technology and features in a consumer-friendly ‘push-to-know’ digital display that allows patients to record and review their last 16 insulin doses, including the priming doses.

Oral treatment for breast cancer
GlaxoSmithKline launched its first oral treatment for advanced breast cancer in Singapore. The first oral ErbB1 (EGFR) and ErbB2 (HER2) dual inhibitor, ‘lapatinib,’ received Health Sciences Authority (HAS), Singapore approval for use in combination with capecitabine for the treatment of patients with locally advanced or metastatic breast cancer whose tumors over expresses ErbB2 (HER2) and have received prior therapy, including trastuzumab.

Lapatinib is a dual tyrosine kinase inhibitor targeting both ErbB1 (EGFR) and ErbB2 (HER2) receptors, and preventing the downstream signaling events essential for cancer cell proliferation and survival. This innovative mechanism of action is a new way to treat breast cancer and is different from current targeted therapy for ErbB2 positive disease.

Smallest ultrasound device
Barely larger than a Blackberry and weighing just a little more than 700 grams, a new portable ultrasound device Acuson P10 from Siemens Medical Systems, supports medical personnel in emergency efforts. This handheld device is intended for complementary initial diagnostic care and triage, particularly in cardiology, emergency care and obstetrics.

It is poised to change the physical exam by providing immediate information to health care providers at the earliest possible patient intervention points, such as intensive care units, ambulances and medical helicopters. In emergency situations, for example, this translates into earlier, faster and more accurate screening and triage decisions. Its emergency applications include FAST (Focused Abdominal Sonography for Trauma) for detecting fluid, determining cardiac activity and pericardial effusion as well as for detecting abdominal aortic aneurysms and performing
pelvic exams.

A big leap for Indian enterprises
Year 2007 saw India-based Bharat Biotech International launch BioHib, the first indigenously developed and manufactured Haemophilus Influenza type b (Hib) vaccine in India. It also launched its tetravalent combination vaccine, Comvac4-HB containing Diphtheria, Pertussis, Tetanus and Hepatitis B in one vaccine. These two new vaccines BioHib and Comvac4-HB, enable the deployment of a combination pentavalent vaccine in a single injection.

India’s No. 1 biotechnology company and vaccine manufacturer, Serum Institute of India, earlier this year, launched its indigenously manufactured low-cost Haemophilus influenza type b conjugate vaccine under the brand name of HibPRO in India. HibPRO has been priced at $9 (Rs 375) for a monodose vial. HibPRO is a vaccine with clinically proven efficacy and safety at an affordable price.

India’s pharma major Dr Reddy’s Laboratories has launched Reditux, the Dr Reddy’s brand of rituximab, a monoclonal antibody (MAb) used in the treatment of Non-Hodgkin’s Lymphoma.

Talking about monoclonal antibody-based drugs, India’s biotech major Biocon’s BIOMAb EGFR for treating solid tumors of epithelial origin has extended applications. BIOMAb-EGFR that was launched in September 2006, has in 2007 seen an increase in the total number of registered patients to almost 1,000 in the country. The drug indicated for head and neck cancer is also being studied in global clinical trials for colorectal, lung cancer, glioma (brain cancer), and pancreatic cancers.
(A special feature on vaccine czars of India on page 36)

Exubera flops
Pfizer’s Exubera got certified as one of the biggest dud in the modern pharmaceutical history. The company forecasted sales of at least $2 billion a year but the reported revenue amounted to just about $12 million in the last nine months.

People Round up 2007 
A Nobel Prize for gene targeting

Dr Mario R Capecchi, Dr Martin J Evans and Dr Oliver Smithies were honoured with this year’s Nobel Prize for medicine for their discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells”.

These Nobel Laureates have made a series of ground-breaking discoveries concerning embryonic stem cells and DNA recombination in mammals. Their discoveries led to the creation of an immensely powerful technology referred to as gene targeting in mice. It is now being applied to virtually all areas of biomedicine—from basic research to the development of new therapies.

Gene targeting is often used to inactivate single genes. Such gene “knockout” experiments have elucidated the roles of numerous genes in embryonic development, adult physiology, aging and disease. To date, more than 10,000 mouse genes (approximately half of the genes in the mammalian genome) have been knocked out. Ongoing international efforts will make “knockout mice” for all genes available within the near future.

With gene targeting it is now possible to produce almost any type of DNA modification in the mouse genome, allowing scientists to establish the roles of individual genes in health and disease. Gene targeting has already produced more than five hundred different mouse models of human disorders, including cardiovascular and neuro-degenerative diseases, diabetes and cancer.

Dr Mario R Capecchi
Born in 1937 in Italy, he didn’t know how to read and write until he was 9. Later he continued to do his PhD in biophysics in 1967 from Harvard University, Cambridge, MA, USA. Currently he is Howard Hughes Medical Institute Investigator and Distinguished Professor of Human Genetics and Biology at the University of Utah, Salt Lake City, UT, USA.

Dr Oliver Smithies
Born in 1925 in Great Britain he did his PhD in Biochemistry 1951, Oxford University, UK. Currently he is Excellence Professor of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC, USA.

Dr Sir Martin J Evans
Born in 1941 in Great Britain he did his PhD in Anatomy and Embryology 1969, University College, London, UK. Currently he is Director of the School of Biosciences and Professor of Mammalian Genetics, Cardiff University, UK.

Top Invention Prize for Dr Sidhu
Indian-Australian stem cell scientist, Dr Kuldip Sidhu has won the 2007 Top Invention Prize for his pioneering work in stem cells.

Dr Sidhu, an Associate Professor at University of New South Wales, was acknowledged for the work on the derivation of a new human embryonic stem cell line, Endeavour-1.

The prize is awarded by BioMed North Limited, a not-for-profit agency for the management and commercialization of intellectual property generated within the state of New South Wales (NSW).

Dr Sidhu has produced a human embryonic stem cell line without the use of any animal product. This breakthrough eliminates the risk of animal-to-human contamination in potential stem cell therapy treatments. Dr Sidhu’s work could eventually lead to safer treatments for conditions such as diabetes, Parkinson’s disease, spinal cord injury and even breast cancer.

NZ’s first Laureate Awardee
Professor Margaret Brimble, Head of medicinal chemistry at Neuren Pharmaceuticals and researcher at the University of Auckland, is the first New Zealander to receive a Laureate Award for Scientific Excellence from the L’Oréal–United Nations Educational, Scientific and Cultural Organisation (UNESCO) for Women in Science Awards. The Award recognizes her research on the synthesis of biologically active natural products that provide new lead compounds in the development of drugs.

Dr Ge Li, top science talent
Dr Ge Li, Chairman and CEO of Shanghai-based WuXi PharmaTech has received the ‘2006 Top Ten Talents (Science & Technology) in China’ Award. This prestigious award was presented to Dr Li and nine other top scientific minds in the Great Hall of the People, Beijing, China. For the China Talents Award 2006, 100 leading professionals were selected to represent 10 different categories ranging from innovation, science and technology, industry and commerce, to management, and education.