Lunch With the Prez

BIO2003: Reporter's Notebook

Washington, DC.—George W. Bush dropped by for lunch yesterday at the Bio 2003 confab. Some 8,000 participants sat in the vast new Washington Convention Center to listen to what the president had to say about biotechnology.

In the first third of his speech, Bush made it clear that biotech, like all other sectors of society, should shoulder part of the burden for fighting the War on Terror. He urged the assembled biotechnologists to lobby Congress on behalf of his Project BioShield legislation, which would pump $6 billion "over the next 10 years to speed the research, production and availability of effective vaccines and treatments against small pox and anthrax, botulin toxin, E-bola plague and other possible agents of bioterror." Once we got through the war section, he moved on to the much more edifying (at least to me) War on Hunger.

"America and other wealthy nations have a special responsibility to combat hunger and disease in desperate lands," Bush declared. My favorite lines were when the president battered the Europeans for banning biotech crops. "Acting on unfounded, unscientific fears, many European governments have blocked the import of all new biotech crops. Because of these artificial obstacles many African nations avoid investing in biotechnology, worried that their products will be shut out of important European markets," Bush correctly argued. He then thundered: "For the sake of a continent threatened by famine I urge the European governments to end their opposition to biotechnology." Amen, brother!

Most disappointing was Bush's self-praise for pandering to American senior citizens by pushing Congress to adopt a Medicare prescription drug benefit that will end up becoming a federally administered price control system guaranteed to choke off much pharmaceutical research.

Also revealing was his oblique reference to the thorny issue of human embryonic stem cells and research cloning. "As men and women of science you have accepted a moral calling to improve lives and to save lives," he said. "That calling also requires a deep respect for the value of every life. Because even the most noble ends do not justify any means." Translation: Bush believes that embryos consisting of a hundred cells or so are babies, so researchers can't use cells taken from them to cure people of illnesses such as diabetes and Alzheimer's.

Anti-Infectives

Besides big plenary talks with speeches from dignitaries, the BIO conference consists of panels that consider topics ranging from boring (but absurdly important) things like how to get a new drug through the regulatory process, to vital discoveries about how our lives and health are affected by abstruse gene variants lurking in the genomes of living creatures.

My first panel of the day focused on ways to protect food animals and meats from contamination with dangerous pathogens like salmonella and E. coli. One of the long-running issues under discussion is the use of antibiotics as growth promoters in animal feed. Stephen DeVincent, a veterinarian and director of the Alliance for the Prudent Use of Antibiotics, pointed out that 100 percent of chickens and turkeys, 90 percent of swine, 90 percent of veal, and 60 percent of beef cattle receive medicated feed at some point in their lives. The concern is that using antibiotics will create strong and selective evolutionary pressure on bacteria to develop resistance, making them a direct threat to human health because of our inability to control them. As evidence of this growing concern, DeVincent and other panelists cited the decision by McDonald's last week to force their meat suppliers to stop using antibiotics. This carries clout, since McDonald's purchases 2.5 billion pounds of beef, pork and chicken each year.

DeVincent did point out that eliminating the use of antibiotics as growth promoters would raise the price of meats by $1.2 billion to $2.5 billion annually, costing Americans between $5 and $10 per capita. Farmers' profit margins, already slim, would be shaved by a further $0.79 per hog.

Finally, DeVincent pointed out that a recent New York Times editorial opining that antibiotics would not be needed if animals were raised in a healthier way, was a bit off the mark. He cited European research showing that free-range/organically raised animals had a higher prevalence of salmonella, toxoplasmas, and intestinal parasites. Europeans have also found that eliminating antibiotics from animal feed results in the increase of disease bacteria such as campylobacter in meat.

But why does feeding antibiotics to animals promote faster weight gain? Kirk Klasing from the University of California at Davis eliminated the early theories that antibiotics were nutrient-sparing, or that they decreased microbial toxins. The favored theory today is that antibiotics basically prevent flare-ups of the animals' normal gut bacteria, which otherwise divert energy to immune systems rather than producing muscle. They prevent the proliferative ability of all bacteria.

But if we get rid of all antibiotics in animal feed are the farmers out of luck? No, according to Klasing, whose research focuses on a naturally produced protein called lactoferrin and an enzyme called lysozyme, both of which fight bacteria in ways that don't encourage resistance. Lactoferrin is found in breast milk and tears, and is produced by nearly all of our mucus membranes as an initial defense against infection. Klasing fed chickens with rice genetically engineered to express lactoferrin and lysozyme, and their growth rates were comparable to those fed the usual antibiotics.

It turns out that lactoferrin can also be used in post-slaughter applications. A.S. Naidu's company, Activated Lactoferrin, has developed a form of the protein that can be washed over carcasses in a dilute solution for 10 seconds. This process eliminates virtually all bacteria on the meat surface. He claimed that meat treated with his activated lactoferrin would not spoil for nearly 90 days.

Out of such steps is human progress forged.

Splicing Genes

The next panel I attended was devoted to the complex topic of Alternate Splicing in Human Disease. One of the surprises of the Human Genome Project is that the recipe to make a person consists of about 26,000 genes (though this number is not yet firmly fixed). But researchers have found at least three or four times that number of proteins in our bodies. More than half of our genes can be parsed, and in at least two different ways. Genes are not just continuous stretches of DNA that can be read simply, like a sentence. Instead they are much more like acrostic puzzles in which some letters double as letters in multiple words, and from which nonsensical combinations of letters must be eliminated.

The information needed to code a protein is broken up into coding regions, called exons; and non-coding regions, called introns. Biological machines known as spliceosomes then cut out the introns and decode the exons. However, mistakes in pulling out the proper sequences of letters mean that incorrect proteins are made, which can cause diseases.

Richard Einstein, from ExonHit Therapeutics, described how his company can quickly identify alternate splicing problems. ExonHit has identified a compound to treat the degenerative disease amyotrophic lateral sclerosis (ALS), which seems to be the result of an alternate splicing problem. The compound is now being tested in Phase II clinical trials for safety and efficacy.

Hui Wang, from Affymetrix, described how her company is devising new chips that can detect different gene-splicing variants. Now, biochips can contain 2.5 million different probes, and a set of three or four can probe the entire human genome. Otto Edward of Intronn, Inc. described how his company is using gene-splicing therapeutically: Intronn's splicing techniques can cause cancer cells to express diptheria toxin in vitro, which kills them.

The Exhibitions

Another part of BIO 2003 is the vast exhibition space in which companies try to tempt buyers and journalists to drop by. I have to report that one of the dismaying things that hit me was the large number of law firms that had booths at this year's conference. Although I am sure there are exceptions, lawyers and rapid technological progress rarely go together.

I stopped by a few booths to chat with people about what their companies are up to. BioAgri aims to make human medicines in chicken eggs. The company uses sperm to deliver human genes (via artificial insemination) to the eggs, so that the chickens hatched will in turn produce human proteins in their egg whites every time they lay an egg. Today, producing therapeutic human proteins using industry-standard Chinese hamster ovary cells is 10 to 100 times more expensive.

BioAgri also points out that producing proteins in plants might be slightly cheaper, but there are concerns that pharm plants may crossbreed with food plants, causing problems. Also, plants don't tend to fold human proteins into their proper shapes, which lowers their therapeutic value.

Of course, the plant biotech guys have an answer to the chicken biotech guys. A small startup called Biolex in North Carolina uses genetically modified lemna plants, also known as "duckweed," to manufacture human proteins like alpha interferon and human growth hormone. The Biolex lemna system is completely contained within plastic modules, and the plants reproduce clonally; that is, they don't flower and they don't pollinate, so they can't crossbreed with other plants. And no one eats duckweed. Finally, lemna plants can double in size in about 36 hours, which means that one can scale up to produce human proteins very quickly.

The market will decide who wins, but it seems clear that modern biotech production techniques could well end up making medicines cheaper, rather than more expensive.

Today, I will be spending most of my time among the tribe of bioethicists. I will report back what technologies they want to forbid you to have.