14 April 2002

GENETICS WILL NOT LEAD TO MIRACLE CURES FOR DISEASE

"This is almost as irresponsible as what went on in the Nazi era, what this guy is doing. The idea of choosing the perfect child is nonsense" - Professor Nick Hastie, director of the Medical Research Council's human genetics unit at the Western General Hospital in Edinburgh (item 2 - Genetics will not lead to miracle cures for disease)

"...our moral sentiments, when faced with the developments of the last few years, revolt at what may soon be possible: corporate ownership of genetically modified human embryos; the production of living human clones; the use of pre-implantation genetic screening and abortion to select "better" babies; the use of human fetuses as fodder for experiments." - William Kristol (item 1 - The Future Is Now, II)

1. The Future Is Now, II
2. Genetics will not lead to miracle cures for disease, says professor
3. LIFE SCIENCES; CONSULTANTS & THE FUTURE OF HUMANITY.

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The Future Is Now, II

http://www.weeklystandard.com/Content/Public/Articles/000/000/001/097khcjr.asp
William Kristol
The Weekly Standard, April 15, 2002, Vol. 7, No. 30

IN FEBRUARY 2001, after detailing a series of recent "advances" in biotechnology and genetics--genetically modified monkeys, the use of human fetal tissue in rodents, the granting of patents for "hybrid" man-animal embryos, and the harvesting of hearts, brains, and other organs from dead children in a British hospital--we editorialized, "The Future Is Now". The moral and political questions raised by human biotechnology, we argued then, deserve a central place in American public debate.

Much has happened in the fourteen months since:

In the spring of 2001, embryonic stem cells and cloning emerged as central issues in American politics. In June, the House of Representatives passed, by a vote of 265-162, a ban on all human cloning. In August, President Bush, after months of deliberation, delivered his decision about federal funding of embryonic stem cell research in a special televised address to the nation--the first of his presidency. As he put it: "We have arrived at that brave new world that seemed so distant in 1932, when Aldous Huxley wrote about human beings created in test tubes."

In November 2001, Advanced Cell Technology created what were believed to be the first cloned human embryos. When asked whether his technique would eventually be used to clone newborn human beings, Michael West, the company's president, replied: "I'm not an expert in ethics. . . . But, biologically, scientifically, I don't know of any reason why that would not happen." "For the sake of medicine," West added, "we need to set our fears aside."

Now, in early 2002, we read of yet another wave of biotechnological advances. The most shocking was the reported creation by Chinese scientists of cloned human embryos using human DNA and rabbit eggs. Researchers in both the United States and Japan claimed advances in artificial wombs. Advanced Cell Technology reported work on fetal stem cells--not embryonic, but fetal stem cells--taken from cows, raising the specter of such work in human beings. A company named Genetics Savings & Clone announced the cloning of a cat. Other researchers reported the cloning of rabbits "ready in time for Easter." And renegade Italian fertility doctor Severino Antinori claimed last week that one of the participants in his human cloning project is eight weeks pregnant with a human clone.

The list goes on and on, but the lesson is clear: The time really is now. The moment has arrived for setting limits on—and reconsidering--the science that leads to what Francis Fukuyama calls "a posthuman future." Do we want to go down the road of using developing human life as a resource for experiments? Do we want to transform human procreation into a form of technological manufacture? Do we want to design our descendants? How much do we want to modify the chemical and biological workings of brain and body?

It is not always simple to draw lines between genetic therapy and eugenic enhancement, between scientific experimentation and exploitation, between a better human world and a new, inhuman one. But our moral sentiments, when faced with the developments of the last few years, revolt at what may soon be possible: corporate ownership of genetically modified human embryos; the production of living human clones; the use of pre-implantation genetic screening and abortion to select "better" babies; the use of human fetuses as fodder for experiments.

Some lines are difficult to draw. Some are simple and clarifying. In the next few weeks, the Senate will vote on one of the most important--whether to ban human cloning. This vote will set a precedent--one way or the other, for better or worse--for our effort to confront the moral challenges posed by our biogenetic powers. The vote looks likely to be a close one, between two fundamentally different alternatives. One is the Brownback-Landrieu bill, almost identical to legislation already passed by the House. It would ban all human cloning, is supported by the president, and deserves to become law.

The Kennedy-Feinstein and Harkin-Specter bills, which will probably be combined into one alternative, would allow the creation of cloned human embryos for research and destruction. The biotechnology industry and patient advocacy groups have falsely sold this research as the key to imminent cures. They have misleadingly described it in ways that obscure its connection to reproductive cloning (it is the first step down that path) and sanitize its essence (the creation and destruction of nascent human life for research purposes).

Consider this new radio advertisement by the Coalition for the Advancement of Medical Research:

"My name is Kris Gulden. I'm a former police officer and triathlete. Due to a spinal cord injury, I'm now in a wheel chair. In my dreams I still walk and run. And I wake up every morning hoping for a cure. I'm sure someone close to you--someone with Parkinson's or Alzheimer's or diabetes does too. But now we have hope, thanks to a new kind of medical research, called somatic cell nuclear transfer--or SCNT. Some people call it therapeutic cloning, although it has nothing to do with copying human beings."

Of course, it is medical researchers themselves who invented the term "therapeutic cloning." And the supposed promise of this research is precisely that it would create an embryonic copy of human patients in order to provide stem cells that the body's immune system won't reject, or to supply the means to model particular diseases. Apparently the "advancement of medical research" justifies falsification of the facts.

Such sophistry--and the world it portends--must not be permitted to prevail. The Senate now has the opportunity to act to ban all human cloning. If it fails, where will we draw the line? How will we ever summon the will to avert the even darker nightmares that will surely follow?

--William Kristol
[see also: New Genetics, Old Quandaries: Debating the biotech utopia.
by Eric Cohen
The Weekly Standard, 04/22/2002, Volume 007, Issue 31
http://www.weeklystandard.com/Content/Public/Articles/000/000/001/132jmnjg.asp]

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2. Genetics will not lead to miracle cures for disease, says professor

The Herald (Glasgow), April 10, 2002

BREAKTHROUGHS in genetic research will not result in miracle drugs for common diseases or allow people to create designer babies, a leading Scots scientist said yesterday.

Despite the mapping of the human genome, which will allow greater understanding of human biology, Professor Nick Hastie, director of the Medical Research Council's human genetics unit at the Western General Hospital in Edinburgh, said more emphasis should be placed on preventative medicine and health education programmes.

The professor, who heads a government-funded research organisation into genetic research, condemned Severino Antinori, the Italian fertility specialist who claims to be near to cloning the first human baby. "This is almost as irresponsible as what went on in the Nazi era, what this guy is doing. The idea of choosing the perfect child is nonsense," the professor said.

Tonight, he delivers a lecture at the Edinburgh International Science Festival, and said of the claim that with the completion of the human genome sequence, medicine was at the dawn of a new era: "We need genetics to make us understand what makes us human, possibly to understand how the brain works and come up with new drugs and an understanding of disease. "We have been able to identify some genes involved in human disorders and there is no doubt we will have 'smart' drugs that will target individual genes. But people who are saying 'I'm not going to get this disease, my child is going to look like this', are going to be disappointed. Genetics is far too complicated to make all these things possible."

He said the greatest impact on common diseases would be influencing people's lifestyles. Professor Hastie said for the past 20 to 30 years, conditions like diabetes, asthma and obesity had risen enormously. "That is not genes. That is the westernised environment and lifestyle, so we should start with a public health programme to try to reverse the trend. "You won't get the disease unless the genetic variants come together with a particular lifestyle or environment," he said.

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3. Life sciences: Consultants & the future of humanity

Anthony Harrington
Management Consultancy, April 11, 2002

The life sciences arena is a hugely ambitious zone, where controversial research promises Godlike powers to transform and reproduce nature. Anthony Harrington looks at the opportunities in this high growth sector for consultancies and finds that while these are substantial there are also a number of real difficulties - not least the lengthy gestation period necessary before research projects come to fruition. Speed is not something one generally associates with bio-tech companies. By comparison with IT, the life sciences sector seems to run on geological time. Instead of six months from conception to obsolescence, products in this sector regularly take 10 to 15 years to jump through all the R&D and regulatory hurdles on their route to the cash till. Nevertheless, like the sliding of the Earth's tectonic plates, movement in the sector has dramatic consequences. The life sciences arena is a hugely ambitious zone. It has the power to throw up big, world shaking concepts, like cloning and - a little further off - a cure for ageing. It is not just that the emergence of new, wonder drugs can net billions in revenue for the corporations that spin them out, the sector is literally in search of Godlike powers to transform and enhance life. The human genome project and the related field of proteomics, which tries to explain the link between genome sequences and protein structures, have galvanised the whole sector.

However, for the consultancies and IT companies that are looking to target this sector as a potential high growth area, there are a number of real difficulties as well as some obvious opportunities. The first issue is the speed thing. The industry has its own rhythms and they are not the rhythms IT vendors and management consultants are generally happiest with. Playing in the biotech sector means settling in for the long game. According to Mark Hall, director of life sciences research at IDC, it is all about building the kind of relationship with the client that can endure for decades. Not that there won't be the odd "quick win". Certainly, biotech start- ups can be wonderful clients from the outset in that many begin with a need for the kind of computing power you used to find only in meteorological centres and NASA. The bio-sciences are a target rich field for super computer vendors like IBM, Sun and Compaq. Storage vendors also love the sector. Much of a bio-informatics company's first and second round funding can get chewed up by its IT budget as it buys storage farms and scalable SMP servers to crunch the data sets its founders hope will show them the path to the next break-through drug. However, there are difficulties for vendors in getting all their cash up front in this kind of deal. Vendor financing or even equity participation deals are likely to be increasingly common, particularly where the IT is so central a part of the bio- tech company's play.

The risks for the vendors are obvious, and there is a clear parallel here with the telecoms arena during its period of rapid expansion. The consequences of the boom and bust in that sector are still reverberating, in the shape of huge unpaid debts, and mountains of recycled new kit being sold for cents on the dollar. There is already more than a little fear in the biotech market, particularly among investors, many of whom have sobered up after the razzmatazz that swept through the whole bio-tech sector in 2000 and early 2001 over the genome project. When investors take a sober look at the sector they get pulled in two opposing directions. On the one hand, virtually all the start ups are grounded in hard science and have a strong value proposition - which is a lot more than could be said for some of the bubble headed dotcom ideas that went smash. On the other hand, there is that massive gap in time between the inception of a research project and that moment when the bio-tech can start to anticipate a revenue stream ? if some other company doesn't beat it to the winning post. In fact, this last point is so critical that Hall argues that the life sciences arena is going to have to make dramatic changes to its traditional business model over the next few years. "There is just too much work going on now on too many fronts for any company to feel secure in the idea that it has the time to take 15 years to bring a project to fruition. The old model of companies betting everything on one wonder drug that, when it finally appears, will net them billions, has to go," he says. Hall argues that the entire sector needs consultancy help to rethink and reshape its business practices. "It currently takes an average of $800m to bring a drug to market. No one can feel easy taking that kind of bet. We are already seeing a great many more alliances in the sector," he notes. According to Hall, the big manufacturing consultancies may not yet have too many stars from the life sciences arena walking their corridors, but one thing they do understand is how to turn lumbering behemoths into more nimble creatures. The big pharmaceutical companies are already a major target for high end business strategy consultants like McKinsey, while the systems consultancies are all bidding for a larger share of this market. According to Hall, IDC anticipates that the global life sciences market's appetite for IT and consultancy will grow at a compound annual rate of 24%, between now and 2006, reaching a value in excess of $38bn -eye popping growth, by any standards. "What is holding things back right now is that the entire sector is awash with data that is poorly understood. The science is where the barrier is. The most likely scenario, the one that we are basing our growth predictions on, is that the sector will see incremental breakthroughs through the next five years. However, we could also see much more dramatic breakthroughs that really open the floodgates, in which case our predictions may be way too conservative."

IDC has been interested in the life sciences sector for about the last 15 years, ever since it first became visible as an occasional purchaser of super computers. The pace has now picked up to the point where IDC has felt it prudent to formally launch a life sciences division. IBM, for its part, has had a life sciences division for at least the last four years. According to Paul Willer, IBM managing principal, life sciences, IBM puts the current size of the life sciences market for IT and consultancy at around $3.5bn a year, but expects this figure to exceed $50bn "within a few years", making IBM's prediction even larger than IDC's. "We see several drivers for this growth.

Already the R&D teams in the big pharmaceuticals and in many bio-tech companies are hard at work on genomic derived medicines. We are seeing a huge investment in genetic databases to provide the basis for this kind of research.

We also expect a revolution in medicine in this century where we move to a much more fine-grained approach to prescription. For example, Alzheimer's Disease is a named disease today that actually covers about half a dozen different known conditions. You are going to see a much more focused approach to curative medicine coming out of the discovery departments in these companies."

The data issues involved here are huge (see box out overleaf) and IBM is itself placing some hefty bets to ensure that it is at the forefront of research. "We are investing $100m in a super computer called Blue Gene that is going to be 100 times faster than anything the world has so far seen, and it will be aimed squarely at proteomics and genomics," he comments. IBM has a "five year plan" focused on proteomics. This does not mean that it intends to become a bio-tech player. The plan aims to ensure that it is in shape to provide the infrastructure that the sector needs to make its breakthroughs. "We're investing a further $100m in the life sciences as a practice area for our management consulting arm. Here we are looking right across the park.

We'll be doing everything from providing electronic portals for the regulators, to providing enhanced discovery solution. In addition, there are certain roles that require a neutral player to help facilitate integration between all the different databases out there," he says. In all, some $500m of the $6.7bn that IBM spends on R&D every year, will be devoted to furthering the company's play in the life sciences arena, Willer says. Sun is at least as keen as IBM on the idea of selling large computers to the sector.

However, perhaps because its business model keeps it a pure play hardware and software vendor that has to rely on business partners to deliver systems integration and consultancy skills, it has not yet set up a formal life sciences division. Instead it recognises the arena as a "market segment". Suzie Stephens, market segment manager, life sciences at Sun Microsystems, reckons that Sun stays away from the vendor financing and equity stakes game as far as possible when supplying the sector. "Taking equity stakes is a venture capitalist's job, rather than Sun's role. Our big play here, apart from major systems sales, has been to work with BIO, the Biotechnology Industry Organisation to create data standards that will make it easier for the sector to combine diverse databases," she says. This work is now formalised under the I3C, (the Interoperable Informatics Infrastructre Consortium). "Our head of sales has said that life sciences are a $1bn bet for Sun. The market is currently worth around $360m for us and we reckon that we will pass the target of $1bn in annual revenues for this sector within the next three years," she says. The storage that companies in this sector are hanging off large Sun SMP boxes is already massive. One company, Solera, is already talking about getting to 250 Terabytes of store. "The opportunities for our big systems integration and consultancy partners, players like Accenture, Cap Gemini Ernst & Young and PricewaterhouseCoopers, are enormous," she says. KPMG partner Peter May points out that the really awesome fact about the bio-tech sector as things now stand is that its demand for computing resource has completely outstripped the capacity of today's super computers. "We're seeing Moore's Law holding good, with the number of transistors on a chip continuing to double every 18 months, but the simulation demands of this sector as it tries to map from genome sequencing to protein structures, have raced ahead.

 As we go forward the sector's demands will become even more acute and will serve as a massive spur to push the IT sector to new heights," he comments. The consultancy sector, for its part, will have its hands full providing business consultancy advice to the hundreds of bio-tech start ups that are mushrooming in the US, the UK, Europe, Israel, and now in Asia and Japan. "These companies typically have funding for just a few of the 10 to 15 years they are going to need before their product comes to fruition. This means they need multiple rounds of funding through their lives, and corporate finance consultants have plenty of work to do here," he comments. CGE&Y partner Yoram Wilamowski agrees. He has been following the Israeli bio-tech phenomenon for the last five years and points out that consultants who want to get into this space need to realise that companies in this sector take years to mature. The wait, however, is more than worthwhile. "There is a constant upward trend, even in tough times, in most of the parameters in this field, particularly for investors.

 Israel has about 180 companies, including 10 public companies and 25 mid-range businesses. In our experience, despite some flight of capital from the high tech sector to this area, the funding for this sector comes from different sources. Most of the consultancy work we do is traditional business consultancy here, helping them with business strategy and presentation, rather than systems consultancy," he comments. So much has happened in the life sciences that it is easy to forget that this is a very young sector. However, the growth so far has been phenomenal and if the likes of IDC and IBM are right, this sector is going to be worth a very serious "colonising" effort by systems integrators and consultants. PwC does its own BioSciences league table for 39 UK bio-sciences companies. It's table shows the sector substantially outperforming the FTSE All-Share Index through 2001 and, so far, through 2002 as well. Despite the current economic conditions and months of falling share values around the world, the sector is still approximately 116% of its value at 31 December 1999, and 15 of the 39 companies have a higher index than in December 1999. Companies like Amgen are already around the $100bn market capitalisation level, putting them on a par with mid-sized pharmaceuticals, and no one really knows which of the current crop of bio-tech start ups are going to become the next Amgen. The links currently being forged between the giant pharmaceuticals like Pfizer Warner and the bio-techs are themselves an encouragement to the consultants to "get tight" with the current crop of start ups - there is no telling where that trail could lead!

ACAMBIS: THE EXCEPTION THAT PROVES THE RULE

Acambis hit the headlines after 11 September, when the US government gave the UK vaccine bio-tech company a contract to produce smallpox vaccines for the entire US population. Thanks to that contract, Acambis, which was founded in 1992, will be one of only three UK biotech companies to show a profit in 2002 (it's first). According to Acambis director of communications, Lyndsay Wright, while the 200 employee company needs all the usual business infrastructure IT and business orientated consultancy, it has never been, and is unlikely to become, a big consumer of computing resource. "Researching and producing vaccines is a laboratory bench job rather than a compute intensive process. We're a FTSE 250 company, and very proud to be part of the UK's thriving life sciences sector, but we're never going to be a huge target for the IT consultants," she comments. "They'd be better off chasing biotechs specialising in molecular chemistry ..."

THE PROTEIN FOLDING SYSTEM The sequence of amino acids that make up a gene generate a flat, two dimensional string of protein. This flat string is not viable, long term, nor is it particularly useful. Bodies are built from protein molecules with precise shapes. Proteins acquire this shape through a precise series of "folds", crunching down on themselves until they reach their "natural" shape, which scientists now recognise as the shape that requires the least energy to be maintained. Shape, it seems, is the key to "everything" and understanding how one moves from gene sequences to protein structures is a large part of what the bio-sciences are now about. Researchers like Charles Brooks are attacking this problem using super computers to simulate molecular dynamics. For Brooks to run one of his simulations, involving protein folding in myoglobin (a protein that carries oxygen in muscle tissues) on the Pittsburg Supercomputing Centre's CRAY 90 takes a month of computing time with Brooks as the sole user. He is making headway, but his computations only track the protein for about 1.5 nanoseconds. Snapshots of the "folding pathway" taken every millionth of a billionth of a second create 750,000 frames of data for each simulation, or 100 Gigabits of information. These experiments have been criticised as "low veracity" experiments because of the compromises he has to make. To run the kind of simulation he would like, he says, would take the world's current computing resource a few thousand years to execute. This gives an idea of the kind of pressure the bio-sciences are now putting on the likes of IBM and Intel to come up with faster chips.