By Randall Osborne
SEATTLE ¿ As biotechnology firms push for growth ¿ by way of creative financing options, fuller pipelines and multiple partnerships ¿ many of their methods are moving in the other direction.
They¿re getting smaller. And the technology is becoming more exotic, such as ¿nano bombs¿ that fuse to bacteria and explode them, without harming normal, healthy cells.
Nanotechnology is included in the federal administration¿s research and development plan for 2001, noted Gregory Millman, chief of pathogenesis and basic research for the National Institutes of Health in Bethesda, Md.
Potential applications include nanoparticles for drug delivery, miniature sensors for early cancer detection, computer chips that store ¿trillions of bits of information on a pinhead,¿ advanced materials stronger than steel, and artificial photosynthesis for clean energy.
Millman moderated a symposium called ¿Sounds Like Science Fiction? Today¿s Research is Tomorrow¿s Medicine¿ during the Biotechnology Industry Organization¿s meeting and exhibition here, BIO ¿99.
¿It seems appropriate on the day the newest Star Wars¿ movie opens,¿ Millman said, starting the symposium. ¿We¿re all involved in a new enterprise¿ here, and I hope in the next two hours we¿ll boldly go where no one has gone before.¿
Among the presenters was James Baker, professor at the University of Michigan School of Medicine in Ann Arbor and director of the Center of Biologic Nanotechnology, who spoke on ¿Nano Bombs That Destroy Pathogens,¿ which are being developed at the university.
¿We¿re doing cellular engineering, drug delivery, antimicrobial therapy with a whole new set of materials that we have a large proprietary stake in, particularly dendritic polymers and lipids,¿ Baker said.
¿In fact, when you look at the Y2K bugs we really need to worry about, not the ones people talk about, they aren¿t in your computer; they¿re in your environment,¿ he added.
The ¿nano bomb¿ technology is likely to be applicable against various infections ¿ and may be particularly useful against bioterrorism, Baker said.
¿In the U.S. alone last year, there were over 5,000 threats of anthrax attacks,¿ he said. ¿It shut down whole cities at times. Unfortunately, there¿s no real way to deal with those organisms. We can¿t put bleach and formaldehyde, which are about the only things we have to kill anthrax, in the environment. That¿s actually worse than the organism itself.¿
Emulsion Fuses, Then Kills Organisms
The material Baker¿s group is developing is an emulsion. ¿Mayonnaise is an emulsion,¿ he said. ¿An emulsion just means droplets of oil in water.¿
However, the nano-emulsion for drug delivery and gene delivery is unique because its droplets are particularly tiny ¿ smaller than bacteria and viruses, in many cases ¿ and specially engineered, he said.
They ¿are very likely to fuse with bacteria and viruses, while selectively leaving our own cells alone,¿ Baker said. They fuse with membranes and ¿pull out the lipids and pull out the proteins.¿
Some nano-emulsions fuse only with bacteria, which ¿doesn¿t actually explode it, as we suggested, but disrupts the structure of the organism, and you can see a change that occurs that kills the organism de facto.¿
Other structures ¿actually will like the organism, so that when they fuse, they will disrupt so much of the protein in the membrane that the organism literally explodes.¿
It happens almost immediately. ¿We actually have to freeze these after less than a minute, to see any intact organisms left,¿ Baker said.
The material works against HIV, influenza, smallpox, herpes simplex ¿ ¿any type of envelope virus,¿ Baker said. ¿Even Ebola.¿
Dan Branton, professor in the department of molecular and cellular biology at Harvard University in Cambridge, Mass., spoke on ¿Warp Speed DNA Sequencing,¿ a developing method to sequence a strand of DNA by identifying each base as it passes through a nanopore.
Introducing him, Millman asked the audience to ¿imagine a chip containing 500 pores, reading at 1,000 bases per second. Such a chip could theoretically read an entire human genome in two hours, or the genome of the pathogen in a few seconds.¿
Faster Sequencing Key To Exploiting Technology
Branton said there are ¿many who disagree with the current emphasis on sequence information in the Human Genome Project.¿ He quoted Freeman Dyson¿s remark that it¿s ¿reprehensible¿ to use public funds and private resources to gain sequence information before perfecting methods for high-speed sequencing.
¿While I wouldn¿t agree with his use of the word reprehensible,¿ I think it is clear that, as we moved toward individualized medicine, the days of gel sequencing, currently used for sequencing DNA, are going to have to be replaced by much faster methods,¿ Branton said.
¿The physician of tomorrow is, in frequent cases, going to expect information to go far beyond an analysis, for example, by single nucleotide polymorphisms,¿ he said. ¿He¿s going to expect he can find additional answers about his patient by looking at detailed sequencing information, but he¿s going to expect that information in the time course that, today, he can order a cholesterol test.¿
Branton¿s method is ¿based on the very simple notion that, if you have a membrane separating two compartments filled with salt solution, and you pass a voltage across this membrane, ions will flow through a channel if you have a channel in the membrane.¿
¿Now, if we place DNA in one of these compartments, and maintain a voltage gradient such that this side is negative and this side positive, the negatively charged polymer of DNA will be drawn through the channel, we speculated, and, as it moves through the channel, will block the passage of ions, diminish their flow through the channel.¿
Measuring the activity then could make a sequencing picture.
¿What we¿re interested in is the blockage as the DNA moves across the channel,¿ he said. ¿Within these details, we hope to see differential ionic flow [that is] a result of the chemical and physical properties of each base, as it flows through the limiting aperture of the channel.¿
The goal is ¿base discrimination using these nanopores¿ ¿ which will be made, ¿if possible, of an inorganic substance,¿ Branton said.
The BIO ¿99 meeting continues through today.