Senator Bill Frist's Biological "Manhattan Project"

Senate Majority Leader Bill Frist has joined the call for a major program to advance scientific and technical capabilities in biology.

In remarks at Harvard Medical School on 1 June, 2005, he called for a new Manhattan Project(PDF).  This isn't the best analogy to make, given the connection to secret weapons programs, but the right sentiment is there nonetheless.  I strongly prefer the Apollo Program as an analogy, particularly if you re-frame the cold war competition angle as a race against pandemics and bioterrorism.

UPDATE (5 June 05): Here is what I wrote in 2003 about the Manhattan and Apollo Project as analogies for a big biological program;

Previous governmental efforts to rapidly develop technology, such as the Manhattan and Apollo Projects, were predominantly closed, arguably with good reason at the time. But we live in a different era and should consider an open effort that takes advantage of preexisting research and development networks. This strategy may result in more robust, sustainable, distributed security and economic benefits.  Note also that though both were closed and centrally coordinated, the Manhattan and Apollo Projects were very different in structure. The Apollo Project took place in the public eye, with failures plainly writ in smoke and debris in the sky. The Manhattan Project, on the other hand, took place behind barbed wire and was so secret that very few people within the US government and military knew of its existence. This is not the ideal model for research that is explicitly aimed at understanding how to modify biological systems. Above all else, let us insist that this work happens in the light, subject to the scrutiny of all who choose to examine it.

Anyway, Frist's comments constitute, by my reading, a major domestic and foreign policy speech.  A speech to frame a political career, you might say.

A few paragraphs:

"I propose an unprecedented effort – a “Manhattan Project for the 21st Century” – not with the goal of creating a destructive new weapon, but to defend against destruction wreaked by infectious disease and biological weapons.  I speak of substantial increases in support for fundamental research, medical education, emergency capacity and public health infrastructure; I speak of an unleashing of the private sector and unprecedented collaboration between
government and industry and academia; I speak of the creation of secure stores of treatments and vaccines and vast networks of distribution; I speak of action, without excuses, without exceptions; with the goal of protecting every American and the capability to help protect the people of the world.

I call for the creation of the ability to detect, identify, and model any emerging or newly emerging infection, present or future, natural or otherwise; for the ability to engineer the immunization and cure, and to manufacture, distribute, and administer what we need to get it done and to get it done in time. For some years to come, this should be a chief work of the nation, for the good reason that failing to make it so could risk the life of the nation and other
nations the world over.

This is a bold vision.  But it is the kind of thing that, once accomplished, is done. And it is the kind of thing that calls out to be done, and that, if not done, will indict us forever in the eyes of history. In diverting a portion of our resources to protect nothing less than our lives, the lives of our children, and the life of our civilization, many benefits other than survival would follow in train, not least the satisfaction of having done right.  If the process of scientific
discovery proceeds as usually it does, we will come to understand diseases that we do not now understand and find the cures for diseases that we cannot now cure. And, as always, disciplined and decisive action in facing an emergency can, even in the short run, compensate for its costs – by adding to the economy both a potent principle of organization and a stimulus like war but war’s opposite in effect.  This would power the productive life of the country into new fields, helping transform the information age with unexpected rapidity into the biotechnical age that is to come.  All this, if the nation can be properly inspired in its own defense and protection, perhaps just in time.

We have built great cities, dams, and aqueducts. We have built the interstate highway system, bridges, canals, fleets, armies, a world of structures. We have decided upon going to the moon and then done so in a few short years. Can we not, then, build this thing, and take these steps, to protect our lives and the lives of our children, to evade mass death and suffering, that would strike at all classes, all races, all ages? We must open our eyes to face the single greatest threat to our safety and security today, but also to seize our single greatest opportunity.
 
I am aware of the difficulties. But the United States is as blessed today as it has been since its beginnings. We are the wealthiest, freest, and most scientifically advanced of all societies, the first republican democracy, the first modern state. And although we have suffered criticism of late, we have been willing since our Founding and are willing still to pursue certain ideals. Though not infrequently condemned from the precincts of cynicism, America has mostly left cynics in its wake, sometimes after saving them from floods that they themselves have unleashed."

I can't say I agree with the notion that the vision, "once accomplished, is done."  We might be successful in creating an infrastructure that provides a response capability for both natural and artificial threats, but the work to maintain vigilance and update the technology will never be done.  Nonetheless, we need to get moving.  Right now.

Evidence That GM Crops and Cloned Cattle are Safe

Two papers in the last week contribute data to the discussion about whether GM crops and cloned cows are safe.  The answer is affirmative.  Sorry, Greenpeace; science trumps ideology, at least in this case.  Fortunately, Toto, this isn't Kansas.

"Insect-Resistant GM Rice in Farmer's Fields: Assessing Productivity and Health Effects in China", by Huang et al in last week's Science, describes a controlled study of a field trial that shows clear evidence for a reduction in use of pesticides, higher crop yields, and improved health of the farmers.  Receipt of GM and non-GM strains for planting was randomized amongst participating farmers, facilitating analysis of the effects of genetic modification.  The results speak for themselves:

This study provides evidence that there are positive impacts of the insect-resistant GM rice on productivity and farmer health.  Insect resistant GM rice yields were 6 to 9% higher than conventional varieties, with an 80% reduction in pesticide usage and a reduction in their adverse health effects.  Such high potential benefits suggest that produces from China's plant biotechnology industry could be an effective way to increase both competitiveness internationally and rural economies domestically.  The benefits are only magnified if the health benefits are added.

There has been considerable discussion about the health and economic impacts of GM food crops, with neither side having much data on their side.  This is particularly important for China, because they want to commercialize both strains studied in the field trial, which makes any uncertainty a threat to success in the market.  Now, however, the evidence indicates GM food crops are both safe and economically superior.

And it isn't just biotech plants that are proving safe.  In a paper in last week's PNAS, Tian et al studied the composition of milk and beef from cloned cattle.  Milk from the cloned cattle was virtually identical to control animals as determined by measuring fat content, lactose content, and protein composition.  The beef cattle were cloned from a bull chosen because of a high fat marbling score; unsurprisingly the clones demonstrated a high fat content as well.

The authors note that while only small number of animals were studied in this pilot project, "most parameters of the composition of the meat and milk from somatic animal clones were not significantly different from those of their genetically matched comparators or industry beef comparators, and that all parameters examined in this study were within the normal range of beef and dairy products approved for human consumption".

Broken Drug Development Model

Sam Jaffe's article in Technology Review, "A Dip in Time", discusses some well known problems with the pharmaceutical industry.  Namely that it costs a ridiculous amount of money to get a drug into testing, which is just the beginning of the financial gamble because it is so hard to predict how new compounds will behave in a large and complex population.  More interesting for me is the suggestion -- within the first sentence, even -- that, "Some [are speculating] that the way new drugs are financed and brought to market will soon be overhauled".

With venture firms basically gambling that one or two in ten investments will pay for the rest, we certainly can't expect innovation from that direction.  Alas.

The article ends with a note that Millennium Pharmaceuticals is using genetic/genomic screening to choose which patients to include in drug trials.  This will certainly help with the trials, but it is rather a backwards strategy to take what you happen to have on hand and see who benefits.  That said, this is what most companies have to work with, and they are looking out for the bottom line first and foremost.  It is clear some significant effort needs to be put in to changing the whole drug discovery and testing infrastructure, so that it is a bit more rational at the front end.

Richard Meagher and Phytoremediation

Richard Meagher, at the University of Georgia, is doing some excellent work using plants to clean up toxic materials in soils, a technology otherwise known as phytoremediation.  Meagher's lab genetically modifies plants and trees so that they express a bacterial gene that helps metabolize complex mercury and arsenic compounds.  His team has achieved impressive results, some of which was described in National Geographic's Strange Days on Planet Earth.

Another biological chassis and power supply

If you want to build new widgets using biology, you need to work with cells amenable to the task.   Tom Knight, at MIT, prefers the innocuous insect commensal bacterium Mesoplasma florum as a prototype biological chassis and power supply for genetic circuits.

After reading my article on garage biology in this month's Wired, David Metzgar, at the Naval Health Research Center, sent me a paper describing another candidate organism, Acinetobacter ADP1.  The paper describes ADP1 as naturally competent for genetic transformation and that it has a "strong natural tendency towards homology-directed recombination."  That is, it likes to harvest DNA from its environment and incorporate it into its genome.  Metzgar writes that, "The close relationship between E. coli and ADP1, combined with the newly available whole genome sequence of ADP1, allows the tremendous amount of existing knowledge related to gene function and metabolism of E. coli to be applied directly to ADP1."  They ported a variety of genes directly from coli to ADP1 without modification.

Since it is common, easily grown, and poses no pathogenic threat to humans, this could be a useful bug.

Technology transfer to middle school students

The upcoming 86th ANNUAL MEETING of the AAAS Pacific Division will be in Ashland, OR, June 12-16, 2005.  There will be a couple of workshops put on by Bio-Rad to help teachers understand how to use various kits within the classroom.  From the looks of it, some fairly sophisticated technology is now being introduced to students as early as middle school.  No genetic modification, but the workshops cover tools everyone uses in the lab to understand the systems they are working on, or systems they are building.

From the Meeting Schedule:

Bio-Rad Corporation of Hercules, CA, is presenting the following five hands-on workshops to give middle school, high school and university instructors the opportunity to try out some of the molecular biology kits they offer to educators. There is no charge for these workshops. However, participants must be registered for the meeting. Be sure to wear your meeting badge to each session. Space is on an “as available ” basis and preregistration is not required. Bio-Rad representatives will provide certificates of attendance for those desiring to utilize these workshops for professional development credits.

Wednesday, June 15

8:30 a.m.Genes in a Bottle. Extract and bottle your own DNA. Introduce your students to molecular biology with their own DNA! In this activity, you will extract and bottle the DNA from your own cheek cells to make a necklace. This real-world laboratory procedure is used to extract DNA from many different organisms for a variety of applications and integrates multiple life science standards in a single lesson. Seeing DNA makes it real. Be the first at your school to wear your DNA!

10:30 a.m. ELISA Immuno Explorer. Biology's magic bullet. Explore immunology with this topical, new hands-on classroom lab.ELISA (enzyme-linked immunosorbent assay) is a powerful antibody-based test used to detect diseases such as HIV/AIDS and SARS, and to trace pathogenic agents in water, food, and the air whether these emerge naturally or through acts of aggression. You will simulate the spreading of a disease, perform ELISA, and learn how this assay is used to identify and track agents of disease , or to detect molecular markers of cancer, pregnancy, and drug use. This kit integrates multiple standards in a single lesson, including antigen-antibody interactions and the role antibodies play in medicine, epidemiology, and biotechnology.

1:30 p.m. PV92 PCR. What pair of genes are you wearing? PCR is central to forensic science and many medical, archaeological, and ecological procedures. You will extract DNA from your own hair samples, then amplify and fingerprint a pair of alleles, an Alu repeat within PV92, a real forensic marker. This activity integrates multiple life science standards in a single lesson and covers a range of core content areas, from DNA replication to evolution to Hardy-Weinberg equilibrium theory.

Thursday, June 16

9:00 a.m. GMO Investigator/Analysis. Have your favorite foods been genetically modified (GM)? Currently, genetically modified organisms (GMOs) in foods do not have to be labeled in the US. Regardless of where you stand in the GM debate, wouldn't it be fun to know if the corn or soy-based foods you eat are GMO foods? This kit uses DNA extraction techniques, PCR, and gel electrophoresis to test common grocery store food products for the presence of GMO foods. This activity integrates and reinforces multiple life science standards in a single lesson.

1:00 p.m. Protein Fingerprinting. Can molecular evidence support evolution? DNA gets a lot of attention but proteins do all the work. Proteins give organisms their form and function and are the raw material for evolution because natural selection acts on phenotypes. Over time, accumulated changes in DNA (genotypes) lead to variation and ultimately, speciation. You will extract muscle proteins from both closely and distantly related species of fish and use protein electrophoresis to generate protein fingerprints to look for variations. This activity integrates multiple life science education standards in a single lesson from physiology to the theory of evolution to exploring the molecular framework of biology. DNA>RNA>Protein>Trait.

Geographical Distribution of Biological Technologies

I just stumbled over William Hoffman's World Stem Cell Policy Map, which shows the geographical distribution of policy about stem cells and major genome sequencing centers.  It is part of a larger project to create Global Maps of Human Technological Development, including Global Biotechnology Clusters and Global Biotech Crops.

With the amount of cutting edge research and development taking place in China, India, Taiwan -- the list goes on -- it is interesting to see things laid out this way.  I have concentrated mostly on how technologies are changing in time, and on constructing analogies to help understand what sorts of technologies we need to do better biology.

But the geographical perspective is instructive.  There are obvious clusters of research, some of which lie in countries that are dramatically more permissive about clinical trials than is the US.  It wouldn't take that much in the way of resources to plunk down a cutting edge center in most of the blank areas of the map.  I hope Mr. Hoffman keeps things updated so we can see how the maps develop.

Stem Cell Therapy in India

The 17 March, 2005, issue of Nature has a story titled, "Indian regulations fail to monitor grown stem-cell use in clinics", by K.S. Jayaraman.  The article explains that guidelines for research will be discussed soon, though stem cell are already being used in clinics.  It is yet another indication of how readily new biological technologies will be adopted as soon as they become available.  Like the clinical use of stem cells in Russia, the article notes there appears to be little central awareness of which studies are being performed where.  The "nation's premier medical institute" is pursuing clinical applications of stem cells for treating a variety of conditions without governmental knowledge or approval.  The article notes that, "The quality of cells being used in therapy is of major concern, as is the failure of clinicians to understand basic stem-cell biology."

If these treatments do show promise, I wonder how quickly US and European regulators will move to get clinical trials underway, or if they will insist that treatments on this side of the world be derived from a more basic understanding of mechanisms.  That will definitely slow things down.