Tuesday, July 24, 2007

Friday, July 20, 2007

A mother's race for a cure




One entrepreneur plunged into biotech to save her daughter's life.

It took a few years before Martine Rothblatt got used to describing her daughter's chronic lung disease as a lucrative market opportunity. "I choked every time I said it - it sounded so immoral," says Rothblatt, 52. But when she realized that the fastest track to a cure was to launch a biotech firm and then take it public, Rothblatt started United Therapeutics (unither.com).

That was in 1996, and today she is convinced that capitalism is the answer. "I no longer have any doubt about the benefit of using profit motivation to develop cures," she says. "It's the language I need to build the company," she says. "It's the language that Wall Street understands."


United Therapeutics founder Martine Rothblatt at her office in Silver Spring, Md.

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After four consecutive years of growing annual revenues by about 40 percent, Rothblatt has proved to be a deft linguist. United Therapeutics (Charts), No. 22 on the FSB 100, reported $159 million in revenues last year. The company, based in Silver Spring, Md.,makes and sells Remodulin, a drug that treats pulmonary hypertension (PPH), abnormally high blood pressure in the arteries that supply the lungs. The rare, incurable, and often fatal ailment causes shortness of breath, fainting spells and fatigue. Most treatment options, ranging from daily pills to intravenous medicines, are fully reimbursable by insurance companies.

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Sitting beneath bright paintings of DNA strands bursting from planets and stars, commissioned by Rothblatt for her company's headquarters, she describes watching her daughter, Jenesis, battle PPH when she was diagnosed as a little girl. Jenesis survived on a mix of pills, but doctors warned that if her condition worsened, she would have to take Flolan, a GlaxoSmithKline (Charts) drug that stays in the bloodstream for only three minutes. It must be continually administered via a catheter threaded directly into the groin or neck. Unstable at room temperature, Flolan requires patients to carry an ice pack 24 hours a day to ensure that it stays cool.

"The treatment seemed worse than the disease," recalls Rothblatt, stroking one of the three mohawked Labradoodles that roam her offices. "My vision became an inhaled version of the medicine." Her first step was to develop a drug that lasted longer than Flolan.

Rothblatt had no background in biotech: She had started her career as a corporate lawyer and gone on to help launch three successful satellite-communication companies, including Sirius Satellite Radio (Charts). In 1995, Rothblatt sold some of her telecom stock and used the proceeds to fund nonprofit PPH research. But after spending $2 million over two years, she saw little progress and grew discouraged.

She started researching the disease herself and found more than just a potential treatment - she found a business opportunity. The National Institutes of Health estimates that more than 200,000 suffer from PPH worldwide. Each patient pays as much as $150,000 a year for treatment - a $7.5 billion market in the U.S. alone.

After selling her vision of an inhaled PPH therapy to angel investors, Rothblatt tracked down and recruited two scientists who had developed a promising PPH drug at Burroughs Wellcome before it merged with Glaxo in 1995. It took Rothblatt seven months to license the compound, which Glaxo had shelved in favor of Flolan. Rothblatt founded United Therapeutics in 1996 and took the company public three years later.

Reaching her goal of developing an inhaled drug would take years of clinical trials, and Rothblatt had to find a way to keep investors happy in the meantime. "Something I learned from my satellite companies - you have to develop iterations of your products over time, producing real revenues incrementally," she says.

In 2002 the FDA approved the company's first version of Remodulin, the compound she licensed from Glaxo. Remodulin, which patients inject under their skin, lasts as long as three hours in a patient's bloodstream and doesn't have to be cooled. The drug, say some pulmonologists, is easier and safer to administer than Flolan. Neither a spokesman for Glaxo nor one for the drug's U.S. distributor would comment on the ease and safety of the use of Flolan.

United Therapeutics in 2004 introduced the drug in an IV form that is less painful to inject than the original version. Later this year the company hopes to complete clinical trials on the inhaled and tablet forms of Remodulin, which are expected to hit the market in late 2008 and 2009, respectively. But Rothblatt faces a lot more competition today. At least four companies now offer PPH drugs. One, Ventavis, is an inhaled medication produced by Actelion (actelion. com), a San Francisco biotech firm.

Ironically, the young girl who inspired Rothblatt to found United Therapeutics has not benefited from the company's work. Jenesis Rothblatt is 22 today and still takes pills for her PPH (her condition never became severe enough to require Flolan or Remodulin).

Rothblatt, a transsexual, pursues many interests outside biotech. She has published four books, including "The Apartheid of Sex: A Manifesto on the Freedom of Gender" (Rivers Oram Press, 1996) and "Two Stars for Peace" (iUniverse, 2003), in which she argues that the U.S. could bring peace to the Middle East by granting U.S. statehood to Israel and Palestine. She also sits on the boards of several organizations that study the use of technology to extend human life.

Yet her primary goal is to grow United Therapeutics by finding treatments for other chronic illnesses neglected by big pharmaceutical companies. The firm's first drug outside the pulmonary market, OvaRex, promises to help keep ovarian cancer in remission (it is in the last phase of clinical trials). Says Rothblatt: "In an industry dominated by dinosaurs, we're going to concentrate on carving out our own little niches, helping the chronically sick live an easier life."

Thursday, July 12, 2007

The President of India DR. A. P. J. Abdul Kalam 's Speech in Hyderabad ..

Why is the media here so negative?
Why are we in India so embarrassed to recognize our own strengths, our achievements? We are such a great nation. We have so many amazing success stories but we refuse to acknowledge them. Why?
We are the first in milk production.
We are number one in Remote sensing satellites.
We are the second largest producer of wheat.
We are the second largest producer of rice.
Look at Dr. Sudarshan , he has transferred the tribal village into a self-sustaining, self-driving unit. There are millions of such achievements but our media is only obsessed in the bad news and failures and disasters. I was in Tel Aviv once and I was reading the Israeli newspaper. It was the day after a lot of attacks and bombardments and deaths had taken place. The Hamas had struck. But the front page of the newspaper had the picture of a Jewish gentleman who in five years had transformed his desert into an orchid and a granary. It was this inspiring picture that everyone woke up to. The gory details of killings, bombardments, deaths, were inside in the newspaper, buried among other news.

In India we only read about death, sickness, terrorism, crime. Why are we so NEGATIVE? Another question: Why are we, as a nation so obsessed with foreign things? We want foreign T. Vs, we want foreign shirts. We want foreign technology.

Why this obsession with everything imported. Do we not realize that self-respect comes with self-reliance? I was in Hyderabad giving this lecture, when a 14 year old girl asked me for my autograph. I asked her what her goal in life is. She replied: I want to live in a developed India .. For her, you and I will have to build this developed India .. You must proclaim. India is not an under-developed nation; it is a highly developed nation. Do you have 10 minutes? Allow me to come back with a vengeance.

Got 10 minutes for your country? If yes, then read; otherwise, choice is yours.
YOU say that our government is inefficient.
YOU say that our laws are too old.
YOU say that the municipality does not pick up the garbage.
YOU say that the phones don't work, the railways are a joke,
The airline is the worst in the world, mails never reach their destination.
YOU say that our country has been fed to the dogs and is the absolute pits.

YOU say, say and say. What do YOU do about it?
Take a person on his way to Singapore .. Give him a name - YOURS. Give him a face - YOURS. YOU walk out of the airport and you are at your International best. In Singapore you don't throw cigarette butts on the roads or eat in the stores. YOU are as proud of their Underground links as they are. You pay $5 ( approx. Rs. 60) to drive through Orchard Road (equivalent of Mahim Causeway or Pedder Road) between 5 PM and 8 PM. YOU come back to the parking lot to punch your parking ticket if you have over stayed in a restaurant or a shopping mall irrespective of your status identity... In Singapore you don't say anything, DO YOU? YOU wouldn't dare to eat in public during Ramadan, in Dubai . YOU would not dare to go out without your head covered in Jeddah. YOU would not dare to buy an employee of the telephone exchange in London at 10 pounds ( Rs.650) a month to, 'see to it that my STD and ISD calls are billed to someone else.'YOU would not dare to speed beyond 55 mph (88 km/h) in Washington and then tell the traffic cop,
'Jaanta hai main kaun hoon (Do you know who I am?). I am so and so's son.
Take your two bucks and get lost.' YOU wouldn't chuck an empty coconut shell anywhere other than the garbage pail on the beaches in Australia and New Zealand .
Why don't YOU spit Paan on the streets of Tokyo ? Why don't YOU use examination jockeys or buy fake certificates in Boston ??? We are still talking of the same YOU. YOU who can respect and conform to a foreign system in other countries but cannot in your own. You who will throw papers and cigarettes on the road the moment you touch Indian ground. If you can be an involved and appreciative citizen in an alien country, why cannot you be the same here in India ?

Once in an interview, the famous Ex-municipal commissioner of Bombay , Mr. Tinaikar , had a point to make. 'Rich people's dogs are walked on the streets to leave their affluent droppings all over the place,' he said. 'And then the same people turn around to criticize and blame the
authorities for inefficiency and dirty pavements. What do they expect the officers to do? Go down with a broom every time their dog feels the pressure in his bowels?
In America every dog owner has to clean up after his pet has done the job. Same in Japan . Will the Indian citizen do that here?' He' s right. We go to the polls to choose a government and after that forfeit all responsibility. We sit back wanting to be pampered and expect the government to do everything for us whilst our contribution is totally negative. We expect the government to clean up but we are not going to stop chucking garbage all over the place nor are we going to stop to pick a up a stray piece of paper and throw it in the bin. We expect the railways to provide clean bathrooms but we are not going to learn the proper use of bathrooms.
We want Indian Airlines and Air India to provide the best of food and toiletries but we are not going to stop pilfering at the least opportunity.
This applies even to the staff who is known not to pass on the service to the public. When it comes to burning social issues like those related to women, dowry, girl child! and others, we make loud drawing room protestations and continue to do the reverse at home. Our excuse? 'It' s the whole system which has to change, how will it matter if I alone forego my sons' rights to a dowry.' So who's going to change the system?
What does a system consist of ? Very conveniently for us it consists of our neighbours, other households, other cities, other communities and the government. But definitely not me and YOU. When it comes to us actually making a positive contribution to the system we lock ourselves along with our families into a safe cocoon and look into the distance at countries far away and wait for a Mr.Clean to come along & work miracles for us with a majestic sweep of his hand or we leave the country and run away.
Like lazy cowards hounded by our fears we run to America to bask in their glory and praise their system. When New York becomes insecure we run to England .. When England experiences unemployment, we take the next flight out to the Gulf. When the Gulf is war struck, we demand to be rescued and brought home by the Indian government. Everybody is out to abuse the country. Nobody thinks of feeding the system. Our conscience is mortgaged to money.

Dear Indians, The article is highly thought inductive, calls for a great deal of introspection and pricks one's conscience too.... I am echoing J. F. Kennedy 's words to his fellow Americans to relate to Indians.....

'ASK WHAT WE CAN DO FOR INDIA
AND DO WHAT HAS TO BE DONE TO MAKE INDIA
WHAT AMERICA AND OTHER WESTERN COUNTRIES ARE TODAY'

Lets do what India needs from us.

Biotech Bonanza

In her close circle, Kiran Mazumdar-Shaw is famous for her outlandish pranks. On April 1 this year she sent friends what looked like share certificates of her Bangalore-based company, Biocon. They were delighted till the significance of the day dawned on them. If only they were real, those pieces of paper could have translated into a small fortune for each of them. For the lady appears to have turned the business of wealth creation into a fine art.

KIRAN MAZUMDAR-SHAW,
50 CEO, BIOCON INDIA



VALUE: Rs 4,843 crore Set up in a garage in Bangalore in 1978, now the country's largest biotech firm spread on an 80-acre campus. She is India's richest woman today

In the rarefied avenues of India's rich and renowned, the path to power has traditionally been paved with steel and silicon, gold and blood. But Kiran proved the exception, bursting into the billionaire club this year from the frothy world of enzymes and genes. Her company's debut at the bourses in April put its value at Rs 4,843 crore. Overnight she was crowned as India's richest women with her personal net worth estimated at Rs 1,900 crore. It also propelled biotechnology, a small knowledge-intensive industry, bang into the league of big business in the country (see accompanying story).

Zipping around Bangalore in her silver E-class Mercedes, with her trademark pearls and scarves, buoyant hair and booming voice, Kiran seems unstoppable and larger-than-life. Her dizzying success only mirrors India's burgeoning prowess in the life sciences. Among Biocon's products are life-saving drugs called statins, which prevent heart attacks by lowering the blood cholesterol level. Given that one in five people in the developed world has high cholesterol, statins have a $20 billion (Rs 92,000 crore) market. Biocon is also developing antibodies and cancer vaccines. "Biocon," declares Kiran, "is a story of ordinary people who thought they could do great things."

The story could as well begin with her and Biocon's slogan: "The difference lies in our DNA". Even as a young girl, she was always racing ahead of the others, breaking barriers, going where angels feared to tread. A topper in science from Bangalore University, Kiran shunned traditional careers and decided instead to become India's first woman brewer and follow in her late father's footstep (her father was a master brewer at United Breweries). Since India did not offer such training, she headed for Australia to study. "Kiran was always independent and confident," recalls her brother Ravi, who is a professor of electrical engineering at Purdue University, US.

When she returned to India in the late 1970s, however, Kiran found that her master's degree in brewing from Monash University could barely make a dent in the glass ceiling in the male bastion that brewing is in India. Women brewers were simply not welcome. Kiran was devastated. In retrospect, though, it may have been the best thing that happened to her.

BIOTECH UNRAVELED

Biotech is an industry that manipulates genes and enzymes, cells and tissues for man's needs.

Modern biotechnology involves processes like genetic engineering and cloning tissues, plants, animals.

Biotech is revolutionising drugs and Biotech unravelledvaccine s production and have brought down costs.

Genetically engineered super plants are expected to boost agricultural yields significantly.

INDIA ON TOP

India is among the world's top 12 biotech powers. The industry is growing at a rate of 25 per cent. India has more biotech companies than Japan, Taiwan or Korea.

By 2010, India is expected to generate $5 billion in revenues from biotech.

The sector will create more than one million jobs in India in the next five years.

Top global companies now look at India as the partner of choice.

In 1978, when biotechnology resided in the realms of science fiction for most ordinary mortals, Kiran, then a 25-year-old with no business experience, decided to turn entrepreneur and use her microbiological training to start Biocon India Ltd. Initially, the firm supplied enzymes to an Irish company called Biocon. Much like Steve Wozniak and Steve Jobs of Apple Computer, she too began in a rented garage on a shoe-string budget of Rs 10,000, manufacturing simple enzymes extracted from sources as eclectic as raw papaya and tropical fish. It is quite a contrast to the glitzy 80-acre Biocon campus on Hosur Road today.

Kiran's success lay in accurately sensing the next opportunity, and capitalising on it early. "She was way ahead of the others in her thinking and vision," recalls close friend Vijay Mallya, the liquor magnate who was one of the few who tapped her expertise. She realised the potential of research outsourcing even in the early 1990s. The Anglo-Dutch multinational giant Unilevers had by then bought over her Irish partner. "As a partner of Unilever's global empire, I became aware of research being outsourced by global giants. And I thought, why not leverage the R&D skills we have in India?" she says. So in 1994, Kiran launched another Indian first-Syngene, a contract research company. Syngene today earns revenues of Rs 40 crore annually, partnering some of the world's biggest drug companies, including GlaxoSmithKline Beecham, Bristol Myers Squibb and AstraZeneca on research projects.



SUPPORT SYSTEM: Kiran with her husband and 'anchor' John Shaw at their Bangalore villa

A fourth-26 per cent-of new biotech companies are following in her footsteps and focusing on "research process outsourcing" (RPO), a term coined and aggressively promoted overseas by Kiran. With an eye typically on the horizon, she has moved to the next potential gold mine-clinical trials. In August 2000, Clinigene was launched to focus on clinical trials. It has already begun clinical trials of oral insulin on diabetes patients. Once again, her business radar is right on track. A CII report estimates the global market for clinical research at $9 billion (Rs 41,400 crore).

Now Biocon is moving into even greener pastures. It will use its technology to manufacture recombinant human insulin. It is a multi-billion dollar market that is expected to revolutionise diabetes treatment and the product will pit Biocon with MNCs like Eli Lilly. Her dream: To propel Biocon into the world's top 10 biotech firms.

It is Kiran's people-centric nature that makes her rise above mundane things like gender differentiation. Her style is hands on and she usually puts in 15 hours of work daily. She insists on being called chairman and not chairperson of Biocon which now employs over 1,100 people (She bought over Unilever's stake in Biocon in 1998 and now owns 39 per cent of the shares). "Our story is of innovation and intellectual wealth creation," she says.

Kiran is also a perfectionist, and a stickler for detail. Almost every plant on the Biocon campus has been personally chosen by her. Pointing to the robust almond tree that grows outside her office window, she says, "I grew that tree with my father's ashes. It is like my father is watching me every moment of my life here."

It's the same sort of care that makes her parties-and she loves throwing them frequently-the talk of the town. A tremendous foodie, she loves fish and seafood. Although she generally likes continental cuisine, Gujarati food lists among her favourites.

Kiran's other great passion is art. She has one of the best art collections displayed both in her office and in her Spanish style villa, Glenmore. But her favourite is a crayon drawing by her 11-year-old nephew Eric. It says, "If I found a pot of gold, I would give it to my aunt for her to make new medicine to fight very bad diseases."

It is her husband John Shaw, whom she met when he was MD of Madura Coats, around whom her universe revolves. "He is my anchor," she declares passionately. After every hectic day, it is with her husband at her side, a glass of her favourite beer or wine and Pavarotti in the background that India's richest woman eases her burdens and dreams a little more.

The Seeds of a Revolution

Raising hopes of creating one million jobs in five years, biotech is already putting India on the world map of great innovators.

Like Kiran Mazumdar-Shaw there is a rapidly growing group of men and women who have hooked their dreams and money to the brave new idea of medicines obtained by tinkering with the processes of life. And like her they are already making pots of money out of it.

V. REDDY,
55 FOUNDER, SHANTHA BIOTECHNIQUES



VALUE: Rs 725 crore*By producing India's first genetically-engineered Hepatitis-B vaccine in his Hyderabad-based laboratory, Reddy brought down its price from Rs 800 per dose to Rs 40.

"Despite the suffocating regulations, we have grown exponentially."

Four years ago, there were only 12 modern biotech companies in India. Today, with almost 100 of them, India is among the top 12 global biotechnology powers, according to Ernst & Young's Global Biotechnology Report 2004. "This is expected to grow 10 times in five years," says CSIR Director-General R.A. Mashelkar. It is already a Rs 1,840 crore industry, growing at a rate of 25 per cent annually. "In India, medical biotechnology dominates," says Sandhya Tewari, director, CII. The number of people employed for research and development in the Indian biotech industry grew by 74 per cent in the past two years. The industry now employs about 10,000 scientists. According to the Ernst & Young report, biotechnology is expected to generate $5 billion (Rs 23,000 crore) in revenues and create more than one million jobs in the country in the next five years.

There is almost a sense of deja vu here. Twenty years ago, when the first it industry survey was carried out by technology magazine Dataquest, it revealed a Rs 100 crore industry with small, unlisted companies and hardly any published data available. Today, information technology is a Rs 75,000 crore industry that gives India a modern identity. The potential is obvious. The world now has what was considered unimaginable even 30 years ago-the blueprint of life, the human genome sequence.

This allows "designer drugs" that can attack the underlying genetic cause of the disease rather than the "one-size-fits-all" synthetic drugs that are currently in use. It is estimated that by 2025, these bio-drugs will replace 70 per cent of conventional therapies. As one scientist puts it, "If we can live the next 25 years, we will be able to live for another 75 years. In the next 25 years, we will be able to design new organs, correct bad genes and fix the problems that eventually lead to ageing and death."

VILLOO PATEL,
48 CEO, AVESTHAGEN GENGRAINE



VALUE: Rs 600 crore* A scientist-turned-entrepreneur, Patel has focused on innovative research and biotech services in pharma and agriculture. Her Bangalore-based company has 49 patent applications.

"Unlike IT, biotech
requires heavy investments in top class R&D."

The impact on India is already visible. In 1997, a young engineer Varaprasad Reddy was shocked when told that India was technologically so far behind that it could not protect its children with vaccines. Determined to make a difference, he set up Shantha Biotechniques in Hyderabad. With scientific assistance from the Centre for Cellular and Molecular Biology (CCMB), it produced India's first "recombinant" vaccine for Hepatitis-B, called Shanvac. This involved inserting the gene for the Hepatitis-B vaccine protein into the bacterial genome. Genes have instructions for proteins in a cell. The bacteria, thinking this gene is a part of their own, produce a large amount of this protein, which can be extracted and purified. Before Shanvac hit the market, the Hepatitis-B vaccine was imported and a single dose cost around Rs 800. Today, the same vaccine costs only Rs 40. It has saved millions of Indians from fatal jaundice.

There has been no looking back. In 2002 Shantha Biotechniques used similar "recombinant" technology to launch an anti-cancer drug, Shanferon, based on a biological substance called interferon. This is the only drug of its kind to be developed, made and marketed by an Indian company. Meanwhile, scientist Krishna Ella, who started Bharat Biotech Ltd International in Hyderabad, used this genetic cut-and-paste expertise to launch a clot-busting drug, streptokinase. This enzyme is a first-line therapy for diseases ranging from acute myocardial infarction to deep vein thrombosis, arterial occlusion and pulmonary embolism.

RAJESH JAIN,
40 DIRECTOR, PANACEA BIOTECH



VALUE: Rs 260 crore Exporting genetically engineered products like insulin and anthrax vaccines, the Delhi-based firm is among India's fastest growing biotech companies and is considered a one-stop shop.

"India is now world class
and can do things just as
well and better."

Reliance Life Sciences of the Reliance Group in the meantime has become a world leader in stem cell research, which could eventually lead to cloning "designer" hearts to replace diseased ones and other organs. In April 2002 Reddy joined hands with Kiran to form a joint venture to produce recombinant human insulin. Beating them at their game, however, was the pharmaceutical firm Wockhardt, which became the first company in Asia to develop, make and market recombinant insulin in 2003. Earlier, insulin cost around Rs 300 per unit. Wockhardt's biotech product made it available at Rs 129 per unit.

If India has benefited from its biotech drugs, the world has too. Indeed that is where the money lies. Up to 60 per cent of India's biotechnology products are exported. The global market for recombinant insulin is valued at $3 billion (Rs 13,800 crore) a year, the interferon market even more than that. As the number of drugs in the developed world come off patent-which means they can be made by anybody-India is ready with the biotech-produced generic versions.

Innovation, rather than copycat products, however, is the true test of the biotech revolution. But progress has been slow. That is because creating intellectual wealth needs physical wealth to begin with. This is an industry marked by long gestation periods. In a sense, biotechnology involves taking a gamble with the processes of life. It requires at least five years of focused, expensive research, before a viable innovative product emerges. And with living processes, there are no guarantees. To stay afloat in the interim, the company would need, other, more reliable sources of revenue.

SWATI PIRAMAL,
47 DIRECTOR, NICHOLAS PIRAMAL



VALUE: Rs 120 crore* The Mumbai-based firm is involved in a range of biotech services, including diagnostics, clinical trials, gene testing, lab services and drugs.

"Biotech takes staying
power as gestation periods
are lengthy."

Indian venture capitalists have traditionally shied away from this sector. But this is changing. In 2003, the Andhra Pradesh Industry Development Corporation (APIDC) set up a venture fund specifically for biotech. When the Insurance Regulatory and Development Authority allowed insurance firms to invest in biotechnology venture funds the Life Insurance Corporation of India invested over Rs 10,000 crore in biotechnology sector. The Technology Development Board has also proposed launching a $40 million fund with the Unit Trust of India, while the Department of Biotechnology has announced its own venture fund of $21 million.

For companies, developing generic bio-drugs is one option that helps earn money which can be ploughed back into research. The second option is to partner more established foreign collaborators. "There is a large opportunity in biotechnology services in India," says Sarath Naru, ceo of the country's first exclusive venture capital firm for biotechnology, the Hyderabad-based Venture Capital. Research service for pharmaceutical MNCs is big business.

In the West, the cost of bringing a drug to the market is $500-800 million and takes up to 10 years. Blockbuster drugs like GlaxoSmithKline Beecham's Zantac made this business feasible. But as drugs go off patent, triggering demands for lower-priced alternatives, the entire pharma industry will undergo major changes. According to Arjun Bedi, partner, Accenture Life Sciences, the routes to survival include specialising in a specific disease or technology area and parcelling out the other stages in drug development.

SUBHASH BAGARIA,
52 CHAIRMAN, MILLIPORE, REAMETRIX



VALUE: Not available Biotech services is where Bagaria saw an opportunity. And he has been proved right with the world buying reagents manufactured by his Bangalore-based companies.

"These are uncharted seas but the challenge is worth it."

This spells opportunity for Indian biotechnology firms. Around a fourth of them are focusing on high-end global research collaborations that are defining Indian biotech. Biocon, for example, partners pharmaceutical big daddies like GlaxoSmithKline and AstraZeneca. "Alliances with foreign partners bode well for the future of Indian biotech," says Utkarsh Palnitkar of Ernst & Young. With highly trained scientists available at a tenth of the cost, western countries are looking to India for survival. India has another gold mine-the world's largest population of "naive" sick patients, on whom no medicine has ever been tried. India's distinct communities and large families are ideal subjects for genetic and clinical research.

A barrier to growth is regulation. This is an industry defined by cutting-edge technology, and the government has just not kept pace. For example, although cloning human beings is banned in several countries and is against ICMR guidelines, it has not yet been outlawed in India. Legal ambiguity has led to a piquant question: can a biotech drug, which is obtained by manipulating living organisms, be treated as any other drug, or does it need to undergo more stringent scrutiny? Biotech is already an industry entangled in red tape. It is governed by five Central ministries and six state ministries. "We need an integrated regulatory clearance system," agrees Kapil Sibal, the new minister of state for science and technology. Clearly, biotechnology is the new frontier to conquer.

India's biotech industry emerging as world innovator, collaborator, competitor

India’s health biotech firms are emerging as a major global player, with growing means and know-how to produce innovative as well as generic drugs and vaccines at costs small relative to those of giant Western firms, according to ground-breaking Canadian research published April 9.

The budding of an innovative Indian biotech sector holds major implications for the global industry and for improving both health and prosperity in the developing world.

“India is innovating its way out of poverty,” says co-author Peter A. Singer, MD, of the McLaughlin-Rotman Centre for Global Health (University Health Network and University of Toronto). “With a massive and increasingly well-educated workforce, India is poised to revolutionize biotechnology just as it did the information technology industry.

“India’s biotech sector is like a baby elephant – when it matures, it will occupy a lot of space. The biotech industry is globalizing rapidly and the impact of India’s market entry and contribution to improving world health is potentially huge.”

However, Singer and co-authors Abdallah S. Daar, MD, Sarah E. Frew, PhD, Monali Ray, Rahim Rezaie and Stephen M. Sammut, MBA, warn that the allure of world market profits may divert much needed Indian research attention away from treatments for specific developing country illnesses, unlikely to be created by Western-based firms. “India needs to take steps to avert this outcome,” they say.

Published April 9 by Nature Biotechnology, the authors say their study of 21 home-grown firms sheds unprecedented public light on India’s private sector biotech efforts and reports “a sector preparing not only for future growth but also, in some cases, for developing innovative products for global markets.”

It is the first known “detailed, independent, publicly available research” revealing product development capabilities and strategies used by India’s private firms to survive and grow amid developing country challenges.

It also recommends ways India and others in the developing world can help domestic biotech firms succeed.

The paper helps set the stage for a Toronto conference May 2-4 at which 20 to 30 North American biotech firms will convene with more than 25 similar firms from India, China, Brazil and Africa – thought to be the biggest-ever assembly of emerging market biotech companies. The goal: to encourage more biotech success and innovation in developing countries and North-South as well as South-South partnerships to address pressing global health problems.

Impacts on drug prices already felt

According to the paper: “The global market for … generic biopharmaceuticals is expected to increase significantly in the next few years as several ‘blockbuster’ drugs lose patent protection. Indian companies appear well positioned to leverage their cost-effective manufacturing capabilities to corner some of this market share and compete on a global scale.”

The paper says the 1997 launch of hepatitis B vaccine Shanvac-B, developed by Shantha Biotechnics of Hyperabad, helped cause a 30-fold domestic price reduction – from about $15 for a comparable imported product to roughly $0.50 – and credits Shantha’s innovative, efficient manufacturing process and well as subsequent local competition.

Shantha today supplies nearly 40% of the UN Children’s Fund’s (UNICEF) global Hep-B vaccine supplies, distributed in Africa, Latin America and elsewhere. Says Dr. Singer: “Think about the impact on health of supplying all that vaccine to UNICEF at those prices.”

Shantha also priced its recombinant interferon alpha (IFN-รก) product Shanferon at about $6.50, undercutting the previous market price for a comparable imported drug by 75%.

The Serum Institute of India (Pune), meanwhile, has become the country’s largest domestic vaccine supplier and exporter, its products reaching 138 countries. The company claims to be the world’s largest measles vaccine manufacturer and, through UNICEF and the Pan American Health Organization, helps immunize half the world’s children against several diseases.

Other examples of a surging Indian health biotech industry: New Delhi–based Panacea Biotec supplies oral polio vaccine to the Indian government and to UNICEF, while the Biocon firm of Bangalore developed a proprietary process for manufacturing human recombinant insulin.

Even before Biocon’s product (Insugen) entered the domestic market, international competitors reduced the Indian price of their products by nearly 40%, the paper says. Biocon priced its product even lower still and says Insugen remains India’s most affordable human recombinant insulin product.

“If the above trend continues, the cost of biopharmaceuticals produced by both domestic and overseas suppliers will continue to decrease as more domestic companies manufacture these products locally,” according to the paper.

It says many Indian firms are scaling up to manufacture such drugs as insulin and interferon, their facilities “refurbished or built in accordance with the standards of international regulatory agencies, such as the US Food and Drug Administration (FDA), European Medicines Agency (EMEA) and the World Health Organization (WHO), to facilitate access to international markets not only for biogenerics but also novel protein products currently in their pipelines.”

“Indian companies are likely to accelerate the development of products for sale in US and European markets, particularly the biogenerics for which they have developed significant manufacturing capacity,” the paper says.

Indian firms are actively pursuing drugs to combat many medical problems, including tuberculosis, encephalitis, malaria, rotavirus, rabies, avian flu, Hepatitus-B, diabetes, cancer, heart disease, cholera, HIV-HCV, tetanus, meningitis, measles and anemia. Other strong areas of interest include combination tests for various medical conditions, as well as antivirals and nutriceuticals.

It adds that India’s domestic firms increasingly need to offer salaries competitive with Western firms to retain talented personnel, potentially impacting the domestic labor pool and research strategies. This trends “may put further pressure on margins of domestic products, and may push companies to shift focus to higher-margin products and services for Western markets.”

North-South collaborations

The paper says some Indian firms use services contracts with overseas firms to fund their operations, develop commercialization capabilities and access valuable international technology and expertise. Services provided include R&D, clinical trials and manufacturing. Bharat Biotech International, for example, is the first developing country firm to manufacture a foreign proprietary vaccine product. It is contracted by the U.S. Wyeth Company to produce its Haemophilis B (Hib) vaccine.

Multi-national corporations increasingly conduct clinical trials in India and rely on Indian contract research organizations to manage these trials. A Bangalore firm, Clinigene, is the first in India with a lab certified by the College of American Pathologists, conducting trials for Merck and Pfizer (USA), AstraZeneca (UK) and others.

Notes co-author Abdallah Daar, MD, of the McLaughlin-Rotman Centre for Global Health: “It will be vital to the industry that Indian companies expanding their capabilities in clinical trials management pay close attention not only to good clinical practice guidelines, but also to bioethical principles, to provide a high level of care and protect the rights of patients.”

R&D alliances between Indian and Western companies have just begun and may be affected by assumptions – correct or incorrect – about the expertise and competence of workers at Indian firms, the paper says.

The paper notes too that major Western pharmaceutical firms, such as Novartis, have recently created their own research facilities in India.

Indian biotech at crossroads

Indian biotech is “at a crossroads,” the authors say, and requires support to maintain it’s original domestic public service orientation.

“It must not only address the significant health needs of its domestic population, but also position itself to take advantage of the often more profitable global marketplace. The country’s health biotech companies operate in close proximity to the shocking disparities in health that plague our globe today. Although these firms are uniquely suited to address these needs, they require financial and political support before they will commit to doing so.”

India’s health system is being hit with a ‘double burden’ of communicable and non-communicable diseases, as basic care improves and the country’s middle class grows, according to the paper.

In 2003, 5.1 million Indians had HIV/AIDS, over 3 million had tuberculosis and 1.8 million had malaria. Approximately 32 million Indians were diabetic in 2000, a number expected to reach 80 million by 2030.

The WHO predicts that by 2015 nearly twice as many deaths across all ages in India will be due to chronic diseases than the combined toll of communicable diseases, maternal and prenatal conditions, and nutritional deficiencies.

“Historically, Indian companies have been the principal providers of medicines and vaccines for the Indian population, enabled by domestic talent and patent laws that protected processes but not products,” the paper says.

Revisions to India’s intellectual property regime, effective Jan. 1, 2005, offering patent protection for products as well as processes, have encourged innovative domestic private sector research programs, the researchers found.

In general, Indian firms are at a relatively early stage in their innovative R&D programs and have “yet to produce a truly innovative health product with the stamp ‘Made in India’,” the authors say.

However, “it isn’t a question of if but when drug product breakthroughs will start arriving from India,” says co-author Sarah Frew.

She says many Indian biotech companies were founded with the purpose of addressing specific local health needs.

“These were often non-innovative products developed with an innovative process and several companies interviewed had success with this business model – both in terms of generating profits and in addressing local needs,” she says.

“Global health authorities want to take advantage of the capabilities of these firms to develop products as well as the social responsibility mandate on which these firms were founded to encourage them to develop products for so-called ‘neglected diseases.’

“We argue that yes, the capabilities are there, but if these companies are not provided political and financial commitments to develop products for these diseases, they too will redirect their focus to developed markets to stay alive.”

The paper suggests India’s government consider identifying a few priority disease areas and create a dedicated fund for commercialization of products related to them.

Barriers to development

Indian biotech executives cite acute risk-aversion among Indian bankers and investors as a barrier to innovation. Says one official: “Early-stage funding for a company that wants to do pure research and go to the market six or seven years later does not exist. There is no money for such a business plan.”

Other barriers to growth identified:

* A poorly coordinated patchwork of Indian regulatory agencies and a slow, confusing approval process that delays health product commercialization;
* A lack of expertise among officials in dealing with biologicals;
* A shortage of advanced training programs and scarcity of qualified personnel;
* The high cost of distribution in rural areas;
* Little entrepreneurial ambition among Indian academics in the biotech sector (resident or returning Indian scientists founded only 4 of 21 firms surveyed).

The paper says the Indian government is ramping up funding and fiscal initiatives significantly to help grow its biotech sector. The Department of Biotechnology’s budget quadrupled in six years, from about $30 to $120 million between 1999 and 2005. And the government has promised to nearly double its science budget – from 1.1% of gross domestic product in 2005 to 2% by 2007.

Fiscal incentives include relaxed price controls for drugs, removal of foreign ownership limits, subsidies on capital expenses and tax holidays for R&D spending.

Other lessons learned

Many start-up firms entered via vaccine markets for which significant local expertise existed and competition from abroad was limited.

Many resourcefully explored various financing opportunities from both domestic and international sources. Often they grew without surrendering much equity, adopting a hybrid business model whereby early revenues were reinvested to expand product and/or service portfolios and relying on project-specific financing from external governmental and nongovernmental agencies.

Successful firms also established and maintained collaborations and partnerships with public and private organizations in India and abroad, establishing global presence through joint ventures with foreign firms or by setting up their own subsidiaries abroad

Finally, several Indian firms are becoming more competitive by patenting products and technologies globally.

“Most people think only of information technologies as the driver behind India’s economic emergence but a lot of innovative research is underway in biotech and other life sciences as well,” says Dr. Daar. “This study documents for the first time what is happening at the individual biotech company level.”

Recommendations for biotech development in India

* Harmonize the pharmaceutical regulatory system into one regulatory agency and ensure adequate training for regulatory personnel.
* Increase training programs in advanced biotech;
* Ensure translation of initiatives in the draft Biotech Strategy into policies that increase effective collaborations between public and private institutions and encourage academic scientists to pursue entrepreneurial ventures to commercialize research.
* Create a favorable and enabling financial environment for enterprise creation and private sector development, including support of early-stage research and product development.
* Identify national priorities for public health and use a targeted funding approach to ensure development of products and services that address local health needs.
* Improve public health infrastructure and/or give incentives to private firms to develop innovative distribution strategies.

Can India's IT Success be Replicated in Biotech?

Active support from the Indian government for increased funds and infrastructure, such as biotech parks, as well as an emphasis on R&D, will help strengthen India's biotech sector in the near future, according to M.K. Bhan, M.D., secretary, department of biotechnology, and R.A. Mashelkar, director general, council for scientific and industrial research.

According to Dr. Bhan, in due time, India will follow WTO regulations. Recently the Indian government approved patent regulations, and under the Trade-Related Intellectual Property Rights agreement, India must implement patent protection on pharmaceuticals and biotechnology products this year.

However, there is strong opposition for the patent bill by political parties and Indian pharmaceutical executives. Those in opposition claim the bill will eliminate the availability of low-cost vital therapeutics to poor countries.

"BioAsia 2005" was held in Hyderabad recently to augment the investments in biotechnology, create awareness about the infrastructure availability in Hyderabad, and facilitate interaction between the different players in the biotech community.

Over 300 participants from across the globe attended, and the chief minister of Hyderabad and the governor addressed the delegates. Over 70 B2B meetings were held and 30 memorandums of understanding were signed during the meeting.


Biotech Parks
As part of the "BioAsia" program, the delegates had an opportunity to spend part of a day at ICICI Knowledge Park near Hyderabad. Several states have taken the initiative to establish biotech parks near major universities.

The state of Maharashtra has set up technology parks, one at Hinzewadi near Pune, and a second for agriculture biotech in Aurangabad. Both of these parks are a few hours drive from Bombay. Over 40% of India's pharmaceutical sales and 30% of all patents filed in India are from companies and academic institutions in Maharashtra.

According to Rajiv Datar, CEO of Shreya Biotechnology (Pune), the 300-acre Hinzewadi park, has facilities for biotech and IT companies. Shreya is building a GMP plant for producing recombinant proteins, including insulin and growth hormone with technology licensed from a U.S. firm.

The focus of new product development in India is in TB, HIV/AIDS, malaria, cholera, cancer, typhoid, and heart diseases.



Vaccines
India is a hub for the vaccine market. In 20032004 it grew at 18.64% and accounted for 47% of the total biopharma segment with sales of US$253 million. GlaxoSmithkline, Wyeth, and Aventis are major multinational players in the Indian vaccine market.

Several domestic players are competing in this market. Major vaccines produced include DPT, DT, BCG, Tetanus toxoid, oral polio, measles, mumps, rubella, hepatitis B, rabies (tissue culture-based), and an injectible typhoid vaccine.

Serum Institute of India (Pune) is the largest global exporter of vaccines and immunobiologicals from India. The company's flagship products are measles and DPT group vaccines, and it is now working on a quadravalent vaccine that will reduce the number of injections for infants to just one. It has established a marketing alliance with Serono in Switzerland.

Shantha Biotechnology (Hyderabad) markets recombinant hepatitis B vaccine and streptokinase. According to V. Reddy, CEO, "India can position itself as an affordable base for producing vaccines for UNICEF and the developing countries and thereby fill the gap left by multinational companies that no longer find the market of pediatric vaccines profitable enough to operate in."

Bharat Biotech is producing Revac-B, recombinant vaccine for hepatitis B, using its HIMAX technology. This process eliminates ultracentrifugation and the use of toxic metals while increasing the recovery of antigenic proteins. Revac-B thus became the world's first recombinant hepatitis B vaccine to be manufactured without the use of cesium chloride. The company also markets streptokinase and is developing a rotovirus vaccine.

Many Indian companies with multimillion dollar revenues in chemical, enzyme, or pharmaceutical areas have also invested heavily in the biotechnology subsidiaries. These include Biocon, Nicholas-Piramal India (Bombay), Panacea Biotech (New Delhi), Reliance, Ranbaxy and Reddy Laboratories.

Nicholas-Piramal has entered into exclusive licensing and co-marketing agreements with global giants like Biogen Idec, Gilead Sciences, and Genzyme.

Panacea Biotech is a leading manufacturer of vaccines. The company's oral polio vaccine received WHO-GMP certification, and its anthrax vaccine is in Phase I trials.

Panacea Biotech has entered joint ventures for vaccine manufacturing with Chiron Vaccines (Emeryville, CA) and thermostable vaccine production with Cambridge Biostability (Cambridge, U.K.). Panacea Biotech is also negotiating a collaboration with ApoLife (Detroit), for using ApoLife's yeast-based technology for the production of therapeutic humanized antibodies.

Wockhardt (Bombay) has an USFDA/EMEA-confirmed manufacturing facility for recombinant biotechnology, and the company is producing three products: Biovac-B (hep B) vaccine, Wepox (erythropoietin), and Wosulin (r-DNA human insulin).


Biotech Start-ups
The biotech sector in India is still a conglomeration of small and medium-sized companies. The major hurdles for biotech start-ups are finding seed capital, regulatory reforms, lack of R&D focus, and intellectual property rights. In spite of those hurdles numerous companies have sprung up in India.

Magene Life Sciences (Hyderabad) is part of M.P. Chary's group of knowledge-based companies. Magene offers a range of contract services from downstream processing to assay development and bioinformatics.

Some of the upcoming biotech companies include Avesthagen, Bangalore Genei, and Gangagen.

Gangagen is developing phage therapy for antibiotic-resistant bacteria. The company has a laboratory in Bangalore and offices in California and Ottawa.

Bacterial phages reproduce upon entering the bacterial cells, subsequently killing the host cell during phage multiplication. This can cause potential problems because of the threat of a sudden release of endotoxins from killed bacteria. Gangagen scientists engineered endolysis-deficient phages, which can kill bacteria without lyses, and the company is developing products for biomedical and agriculture applications using these engineered bacteriophages.



Clinical Trials
India offers great advantages in conducting clinical trials. These include speed of patient enrollment, which is higher than in Western countries, an excellent pool of qualified doctors and investigators, expertise in computer skills like data management, a heterogeneous population, and conformation to ICH and GCP guidelines.

India also provides a unique opportunity to discover the functional significance of human genome sequences because of its genetically diverse patient population.

In addition, because of its IT expertise, India also offers advantages for bioinformatics. With over 76 full-fledged hospitals catering to more then 1,200,000 patients every day, Maharashtra is regarded as a preferred state for conducting clinical trials in the country.

Raptim Research has marketing infrastructure in the U.S. and several European countries, conducts clinical trials for multinational pharma and is growing rapidly, according to Rajan Shah, CEO.

Multinational companies, such as Eli Lilly, are already reportedly spending over 10% of annual turnover on clinical trials in India. According to M.V. Nagendra, M.D., CEO of Asiatic Clinical Research (Bangalore), the biggest share of outsourcing in biopharma will be in clinical trials. He has assembled a competent team of physicians, scientists, and IT professionals, several of whom have returned to India after obtaining experience with U.S. companies.


Financing
At the "BioAsia" meeting, Sandesh Seth, from AmerAsia Capital Partners in New York, outlined a strategy for developing biotechnology companies using the strengths of both India and the U.S.

According to Seth, the U.S. venture capital community is taking a cautious approach toward investing in biotech in India as it is believed that the U.S. biotechnology model is not likely to work in India for the next few years.

Several factors have been cited, including deficiencies in biological testing capabilities and lack of sufficient R&D management talent. However, explained Seth, one of the business models that could overcome these hurdles is for a company to base its front end in the U.S. for R&D management, business development, and financing combined with a back office in India. This could open the doors for U.S. technology and financing while utilizing India's potential in many areas of drug development, clinical trials, and manufacturing.

Alan Levi, CEO of Pfizer (New York City) global R&D, emphasized that globalization of R&D is essential for cost control and acceleration of drug development. India offers not only scientific talent but also many customers for all new drugs.

However, the road blocks are weak IP protection, limited laboratories doing basic research (due to lack of grant programs such as NIH SBIR funds), and lack of an entrepreneurial spirit. Strong commitment and clear vision are needed from the Indian government to resolve these issues.

Friday, July 6, 2007

Thursday, July 5, 2007

Whole Bacterial Genome Replaced

Biologists have successfully transplanted an entire genome from one bacterium to another, replacing the host’s DNA completely and converting it to the donor species. In a study reported in Science online, DNA was removed from Mycoplasma mycoides and inserted into Mycoplasma capricolum, strains that were selected because of their small genome size and fast growth. The success of the study was also facilitated by the close relationship of the two species.

While being an exceptional achievement in genetic and cloning research, this work is also an important development for nanotechnology, and a step towards the goal of producing tiny smart- or nano-machines: Genetic “factories” for biodegradation or biomedical applications.

Mathematical Model Disputes HIV Infection Theory

Researchers at Emory University in Atlanta and the Institute of Child Health in London recently presented a mathematical model that challenges the current theory of how HIV attacks human immune cells. The model indicated that the current “runaway” hypothesis for uncontrolled T cell activation, infection, HIV production and cell destruction, cannot be possible or the disease would progress much more quickly and destroy most T helper cells in a matter of months rather than years.

According to the BBC News, Dr. Jaroslav Stark, from Imperial College London said the research has “thrown serious doubt” on popular theory and that identification of exactly how HIV depletes T cells “could pave the way for potential new approaches to treatment.”

This announcement comes in the same week as the USA National HIV Testing Day, June 27, 2007.

Tuesday, July 3, 2007

Monday, July 2, 2007

ROCKY BALBOA

ROCKY BALBOA

Tuberculosis

Tuberculosis

Large, seemingly useless pieces of RNA - a molecule originally considered only a lowly messenger for DNA - play an important role in letting cells kno

Large, seemingly useless pieces of RNA - a molecule originally considered only a lowly messenger for DNA - play an important role in letting cells know where they are in the body and what they are supposed to become, researchers at Stanford University School of Medicine have discovered.

The finding implies that ancient RNA molecules can orchestrate gene activity across vast portions of the human genome - a cell's genetic blueprint. It also suggests they may be important in cancer development and stem cell maintenance. Overall, the work adds another brick to the growing wall of evidence suggesting that RNA is more than a mere genomic servant.
RNA is best known for ferrying protein-coding instructions from DNA, once thought to be the master molecule of the genome, to the cell's assembly factories. But cracks in this theory began to appear when it became evident that many RNA molecules aren't capable of making protein. While more recent research has shown that small bits of RNA can silence individual genes by interfering with their expression - a la Stanford professor Andrew Fire's recent Nobel work - longer pieces, called non-coding RNAs, have been more perplexing.

"These ncRNAs have long been molecules of mystery," said John Rinn, PhD, a postdoctoral scholar in the laboratory of Howard Chang, MD, PhD, assistant professor of dermatology. "They look just like they should code for proteins, but they don't."

Although ncRNAs have been shown to affect the expression of neighboring genes, the relative abundance of the molecules - accounting for about half of the DNA transcribed in the cell - suggests that they may have a wider sphere of influence than previously thought. Now Rinn, Chang, and their collaborators have discovered that ncRNAs can influence gene expression patterns at distant locations in the cell.

"We were surprised to find that at least one of these molecules can suppress genes on a completely different chromosome," said Chang. "This opens up the whole genome to potential regulation by ncRNAs." The research will be published in the June 29 issue of the journal Cell.
The researchers were investigating how human skin cells, or fibroblasts, know where they are in the body. They had previously shown in different types of cells that groups of genes known as HOX act as a sort of global positioning system by maintaining unique patterns of expression over many generations of cell division. But until Rinn used a new type of gene chip called a tiling array in the new study to home in on nearby regions of DNA, they didn't know how the HOX expression patterns themselves were determined.

"I like to think of it as genomic scuba diving," said Rinn of the new experiments. The tiling array allowed him to map the boundaries of the regions around four clustered sets, or loci, of HOX genes, known as HOXA through HOXD, to near-nucleotide resolution. That's somewhat like zooming in on a single home from a satellite map on Google Earth. "It gives us an up-close, unbiased view of what's actually happening at the chromosomal level," said Rinn.
Not only did Rinn locate many previously unknown ncRNA genes nestled among the HOX genes, he also identified areas that serve as shared landing pads for proteins that either activate or suppress the neighboring regions. "It's a striking pattern," said Rinn. "Like a light switch, the same stretch of DNA can be used to turn genes either on or off, depending on their protein partners." But then Rinn looked more deeply.

The fact that the ncRNAs have remained virtually unchanged over millions of years suggests they may be playing non-traditional but vital roles in gene expression. The researchers found that depleting one ncRNA dubbed HOTAIR, in the HOXC region on chromosome 12 of a skin cell, significantly increased the expression of HOXD genes on chromosome 2. The finding marks the first time that ncRNA has been shown to affect gene expression on a chromosome other than its own.

The researchers believe that HOTAIR functions by affecting chromosomal packing in the nucleus. Inactive chromosomal regions are tightly wound around proteins called histones and cannot be copied into RNA. Loss of HOTAIR in skin cells specifically frees the HOXD control region for binding by activating proteins.

"Next we need to find out how these RNAs work structurally," said Rinn, "and what upstream regulatory molecules might be controlling their expression." They have one clue: HOTAIR binds to and activates a group of enzymes called the Polycomb Repressive Complex 2 that modifies histones and helps them wind up the DNA.

The researchers' interest is more than just theoretical. Polycomb proteins are improperly regulated in some types of cancers. HOX gene expression patterns are likely important to keep stem cells from improperly differentiating into skin, muscle, or other tissues. Understanding how ncRNAs affect these processes will have important implications for cancer therapies and stem cell research, they believe.

"We are really interested in how ncRNA finds its putative target in the genome," said Chang. "There remains a whole level of biological complexity to be explored, including how HOTAIR knows where to go, how it talks to other factors and how it controls histones."
The work will also provide insight into the evolution of gene regulation. Because RNA is thought to have preceded DNA in the evolutionary timeline, it makes sense that it still plays a role in controlling DNA's function.

Rinn and Chang's Stanford collaborators on the research include cancer biology graduate students Jordon Wang and Xiao Xu; surgical postdoctoral scholar Samantha Brugmann, PhD; research assistant Henry Goodnough; and Jill Helms, PhD, associate professor of surgery. Non-Stanford collaborators include graduate student Michael Kertesz and Eran Segal, PhD, at the Weizmann Institute of Science, and Sharon Squazzo and Peggy Farnham, PhD, at the University of California at Davis.

Researchers increase in vivo lifetime of nanoparticles

Researchers at the University of California, Santa Barbara have discovered that attaching polymeric nanoparticles to the surface of red blood cells dramatically increases the in vivo lifetime of the nanoparticles.
The research, published July 7 in Experimental Biology and Medicine, could offer applications for the delivery of drugs and circulating bioreactors.

Polymeric nanoparticles are excellent carriers for delivering drugs. They protect drugs from degradation until they reach their target and provide sustained release of drugs. Polymeric nanoparticles, however, suffer from one major limitation: they are quickly removed from the blood, sometimes in minutes, rendering them ineffective in delivering drugs.

The research team, led by Samir Mitragotri, a professor of chemical engineering, and Elizabeth Chambers, a recent doctoral graduate, found that nanoparticles can be forced to remain in circulation when attached to red blood cells. The particles eventually detach from the blood cells due to shear forces and cell-to-cell interactions, and are cleared from the system by the liver and spleen. Red blood cell circulation is not affected by attaching the nanoparticles.

Attachment of polymeric nanoparticles to red blood cells combines the advantages of the long circulating lifetime of the red blood cell, and their abundance, with the robustness of polymeric nanoparticles, said Mitragotri.Using red blood cells to extend the circulation time of the particles avoids the need to modify the surface chemistry of the entire particle, which offers the potential to attach chemicals to the exposed surface for targeting applications.

The researchers have learned that particles adhered to red blood cells can escape phagocytosis because red blood cells have a knack for evading macrophages. Nanoparticles aren't the first to be piggybacking on red blood cells; the strategy has already been adopted by certain bacteria, such as hemobartonella, that adhere to RBCs and can remain in circulation for several weeks.
The researchers say that it may be possible to keep the nanoparticles in circulation for a relatively long time, theoretically up to the circulation lifetime of a red blood cell which is 120 days if the binding between particles and the red blood cells is strengthened. The methodology is applicable to drugs that are effective while still attached to a red blood cell, although the researchers say that slow release from the red blood cell surface is also feasible.

Mitragotri says this mode of prolonging particle circulation has significant implications in drug delivery, potentially leading to new treatments for a broad variety of conditions such as cancer, blood clots and heart disease.

Five distinct subtypes of alcoholism identified

Analyses of a national sample of individuals with alcohol dependence (alcoholism) reveal five distinct subtypes of the disease, according to a new study by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH).
Our findings should help dispel the popular notion of the typical alcoholic, notes first author Howard B. Moss, M.D., NIAAA Associate Director for Clinical and Translational Research.We find that young adults comprise the largest group of alcoholics in this country, and nearly 20 percent of alcoholics are highly functional and well-educated with good incomes. More than half of the alcoholics in the United States have no multigenerational family history of the disease, suggesting that their form of alcoholism was unlikely to have genetic causes.

Clinicians have long recognized diverse manifestations of alcoholism, adds NIAAA Director Ting-Kai Li, M.D,and researchers have tried to understand why some alcoholics improve with specific medications and psychotherapies while others do not. The classification system described in this study will have broad application in both clinical and research settings. A report of the study is now available online in the journal Drug and Alcohol Dependence.

Previous efforts to identify alcoholism subtypes focused primarily on individuals who were hospitalized or otherwise receiving treatment for their alcoholism. However, recent reports from NIAAA's National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a nationally representative epidemiological study of alcohol, drug, and mental disorders in the United States, suggest that only about one-fourth of individuals with alcoholism have ever received treatment. Thus, a substantial proportion of people with alcoholism were not represented in the samples previously used to define subtypes of this disease.

In the current study, Dr. Moss and colleagues applied advanced statistical methods to data from the NESARC. Their analyses focused on the 1,484 NESARC survey respondents who met diagnostic criteria for alcohol dependence, and included individuals in treatment as well as those not seeking treatment. The researchers identified unique subtypes of alcoholism based on respondents family history of alcoholism, age of onset of regular drinking and alcohol problems, symptom patterns of alcohol dependence and abuse, and the presence of additional substance abuse and mental disorders:

Young Adult subtype: 31.5 percent of U.S. alcoholics. Young adult drinkers, with relatively low rates of co-occurring substance abuse and other mental disorders, a low rate of family alcoholism, and who rarely seek any kind of help for their drinking.

Young Antisocial subtype: 21 percent of U.S. alcoholics. Tend to be in their mid-twenties, had early onset of regular drinking, and alcohol problems. More than half come from families with alcoholism, and about half have a psychiatric diagnosis of Antisocial Personality Disorder. Many have major depression, bipolar disorder, and anxiety problems. More than 75 percent smoked cigarettes and marijuana, and many also had cocaine and opiate addictions. More than one-third of these alcoholics seek help for their drinking.

Functional subtype: 19.5 percent of U.S. alcoholics. Typically middle-aged, well-educated, with stable jobs and families. About one-third have a multigenerational family history of alcoholism, about one-quarter had major depressive illness sometime in their lives, and nearly 50 percent were smokers.

Intermediate Familial subtype: 19 percent of U.S. alcoholics. Middle-aged, with about 50 percent from families with multigenerational alcoholism. Almost half have had clinical depression, and 20 percent have had bipolar disorder. Most of these individuals smoked cigarettes, and nearly one in five had problems with cocaine and marijuana use. Only 25 percent ever sought treatment for their problem drinking.

Chronic Severe subtype: 9 percent of U.S. alcoholics. Comprised mostly of middle-aged individuals who had early onset of drinking and alcohol problems, with high rates of Antisocial Personality Disorder and criminality. Almost 80 percent come from families with multigenerational alcoholism. They have the highest rates of other psychiatric disorders including depression, bipolar disorder, and anxiety disorders as well as high rates of smoking, and marijuana, cocaine, and opiate dependence. Two-thirds of these alcoholics seek help for their drinking problems, making them the most prevalent type of alcoholic in treatment.
The authors also report that co-occurring psychiatric and other substance abuse problems are associated with severity of alcoholism and entering into treatment. Attending Alcoholics Anonymous and other 12-step programs is the most common form of help-seeking for drinking problems, but help-seeking remains relatively rare.

New type of drug shows promise for chronic lymphocytic leukemia

A new type of engineered drug candidate has shown promise in treating chronic lymphocytic leukemia in both test tube and early animal tests, a new study shows.

The agent represents a new class of agents called small modular immunopharmaceuticals. Called CD37-SMIP, the agent targets a protein called CD37 on the surface of these leukemia cells.
The study shows that the agent can successfully attach to the protein on the leukemia cells and kill them. The agent works both by triggering the cells' self-destruction and by causing a particular class of immune cells to attack them.

In an animal model, the agent worked equally as well as the drug rituximab, now routinely used to treat chronic lymphocytic leukemia (CLL) patients. Rituximab targets a different protein on leukemia cells.

The study by researchers at the Ohio State University Comprehensive Cancer Center was published online in the journal Blood.

Our findings have significant implications for the treatment of CLL and related malignancies, says principal investigator John C. Byrd, director of the hematologic malignancies program at Ohio State 's James Cancer Hospital and Solove Research Institute.
Overall, Byrd says,the findings indicate that this could be an effective agent for treating CLL and other malignancies, such as non-Hodgkin's lymphoma and acute lymphoblastic leukemia when they have expression of the CD37 protein.

The laboratory portion of the study used CLL cells from patients, laboratory-grown non-Hodgkin's lymphoma cells and acute lymphocytic leukemia cells.

This research showed that the agent kills leukemia cells directly by triggering their self-destruction through the process of apoptosis.

The study also found that this self-destruction happens differently from how other drugs cause apoptosis. Most drugs cause cells to self-destruct by triggering a cell mechanism that requires enzymes called caspases. This new agent, however, works through a mechanism that does not require caspases.

This is exciting because it means that this agent may benefit patients who are resistant to other CLL drugs, says co-author Natarajan Muthusamy, a research scientist with Ohio State's Comprehensive Cancer Center.It also suggests that it might work well in combination with other drugs, as well as alone.

Stem cell therapy to prevent heart attacks

The use of stem cell therapy to prevent heart attacks is explored in a Comment published in this week's edition of The Lancet.

Professor Harald Arnesen and colleagues from the Ullev?University Hospital, Oslo, Norway looked at studies published to date on the relatively new technique of using of autologous cells derived from bone marrow cells (BMC) to strengthen cardiac function. Autologous cells are sourced from the patient they are used to treat. The authors refer to a trial done in 2002 in which such cells were administered into the heart with encouraging results.

The authors say: "The results of this and several other small uncontrolled studies with the same method were encouraging. However, three randomised trials that tested therapy with BMC were negative for the primary endpoint, improvement in left ventricular ejection-fraction (LVEF)."

A trial of 204 patients (REPAIR-AMI) is also discussed by the Comment authors. Half of these patients were randomised to receive an intracoronary infusion of BMC, or placebo. LVEF increased slightly in the placebo group (47% to 50%) and slightly more in the BMC group (47% to 54%). Despite this modest difference, there was a significant reduction in clinical events in the BMC group compared to placebo - namely that the combined risk of death, heart attack or revascularisation fell by nearly half. Investigators involved in REPAIR-AMI concluded that the results warranted large-scale trials to study effects of BMC infusion on morbidity and mortality.
The authors are concerned about this, because they feel that the methods for measurement of LVEF in REPAIR-AMI were not ideal, and that the positive clinical effect in that trial was driven by poor outcome in the placebo group.

They conclude: "Further research will hopefully develop cell-based treatments that can improve prognosis and quality of life for patients with cardiac diseases. However, because only a small treatment effect has been obtained with inaccurate methods, and because there is reason to question the safety of the placebo procedure in REPAIR-AMI, we think it is inappropriate to invite a large number of patients to participate in new studies based on the methods used in that investigation."

Listeria pathogen may be key to understanding cancer development

A research team including University of Central Florida Microbiology Professor Keith Ireton is using the bacterial pathogen Listeria Monocytogenes to understand the mechanisms of cell growth and cancer development.

In research published this month in the Journal of Biological Chemistry, the team found that a Listeria protein called InlB induces internalization and degradation of a human receptor known as Met. Met has been implicated in the development of some cancers.

Lisa A. Elferink at the University of Texas Medical Branch led the team. She and Ireton found that the ability of InlB to induce Met internalization and degradation requires a human protein called Cbl. If scientists could figure out how to control Cbl, such knowledge might lead to the development of drugs that induce the destruction of Met and are useful in treating Met-related cancers.

Ireton is an expert on Listeria monocytogenes, a cause of food poisoning. He has long studied how it enters into cells of the human body, and explains the mechanism in this month's issue of the journal Cellular Microbiology.

We found that Listeria actually provokes human epithelial cells (cells lining the small intestine) into ingesting bacteria, Ireton said.When Listeria contacts an epithelial cell, the bacterium causes changes in the cell's cytoskeleton that allow the cell to swallow up the bacterium. We discovered that a human protein called CrkII plays a critical role in stimulating internalization of Listeria by somehow controlling the cytoskeleton.

Listeria is a potentially deadly pathogen, causing abortions in pregnant women and meningitis in those with compromised immune systems, resulting in about a 25 percent mortality rate.
The findings are important in helping to understand and control the spread of bacteria that are a cause of potentially fatal food poisoning. Ireton said the bacteria can live outside animal hosts. Sources include dead plant matter, fruits and vegetables, unpasteurized diary products and meats that have not been properly cooked. Pregnant women and people with compromised immune systems are particularly susceptible.

To avoid contamination, Ireton suggests cooking all meats thoroughly, avoiding dairy products that are not pasteurized and washing all fruits and vegetables thoroughly before consumption.