Their Bio Vision

We asked six University of Wisconsin-Madison bioscientists to look into the future and tell us what they’re seeing. You will be interested and maybe even amazed at their vision.

By Nicole Resnick

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As more than 20,000 bioscientists from around the globe convene in Chicago this month for BIO2006, it seems fitting to indulge in a bit of fantasy and reflect on the potentially wider-reaching aspects of the research currently happening at the University of Wisconsin-Madison.

We talked with several leading bioscience researchers at UW-Madison and asked them about their vision for the future. Based on their areas of expertise, we asked them to peer into a crystal ball and got them talking about what they envision — what they hope to see and what they really believe our world will eventually see.

Here, in their words, is what they think about the direction that life sciences research is taking, and what good things the future may hold for us all.

Sussman, “master” of the human genome sequence, admits that ordinarily he would wax eloquent on the impact of human genomics. Yet given this opportunity to think a bit outside his world, he chose instead to talk about something he describes as “more immediate.” As a member of Gov. Jim Doyle’s Consortium on Biobased Industry as well as the Wisconsin Technology Council, Sussman is thinking a lot lately about the subject of biofuels.

“This consortium is looking at how we can strategize to help the state in this emerging area. If plants are going to become a major source of energy for our country, the Midwest is going to play a huge role. And this is a very important area for the economy. As the manufacturing sector decreases and the steel industry ages, biotech is becoming the new focus. Biofuels can translate into billions of dollars. The amount of economic activity involved in biofuels is huge and could be a tremendous boon for our state.

“I like the ideas of biofuels for personal reasons as well because much of my early research and training was in the field of plant molecular biology. The sequencing of the first plant genome, which occurred right before the human genome, has paved the way of understanding plant genomics and has offered a clear strategy for manipulating that. We’re now in a situation where genetic engineering could play a major role as far as plants are concerned, and this could all happen pretty quickly. In fact, it already is happening. Right now, 40 percent of cars in Brazil use ethanol (from sugarcane).

“While it’s become more of a political issue at this point, it is a very interesting situation because politically the teams arealigning themselves in their acceptance of biofuels. Farmers like it, environmentalists like this. Another big problem concerns the release of fossil fuels into the air which contributes to global warming. Corn, however, doesn’t do that — it does not contribute to a net increase in carbon dioxide — and that is a major reason why biofuels are important. If we want to be energy independent, this is the best way to do it. That is, unless solar cells or wind fuel or geo-cells are significantly improved. Until then, the most promising source of fuel is ethanol from a seed.”

“While we have greatly increased our knowledge base, we haven’t yet applied it to solving diseases effectively. While we’ve sequenced the human genome and have made great advances in the field of proteomics, we haven’t really figured out how to solve the diseases that are troubling us. In the future, advances in the development of technology must occur to let us see what is going on inside living cells without destroying them.

“Stem cell technology will be an important contributor to solving disease. With stem cell research I believe we will eventually be able to generate tissues and form organs in vitro. A major research effort, yes — it will take 50 to 100 years — but it will happen. We will learn how to create replacement organs and extend our lives to the 130-year mark, because if the human body if handled right, studies have shown that we should be able to live for 130 years or so.

“With regard to vitamin D research, we have figured out many functions of this molecule, the most obvious being the formation of bone and the regulation of blood calcium and phosphorus. But now we have to learn more about the role of vitamin D in the immune system, in skin, and islet cells of the pancreas. Our research is becoming more focused on what happens when we eliminate vitamin D’s power to raise blood calcium, and this will impact many prevalent diseases such as Type 1 diabetes, multiple sclerosis and inflammatory bowel disease. We are continuing to modify the molecule but the challenge lies in modifying it in such a way as to eliminate one function yet retain other important functions.

“And that is a very interesting aspect of the future of biology and medicine, namely, the use of small molecules such as vitamin D to modify proteins responsible for disease. The next steps will focus on developing such small molecules to tie up the proteins that cause disease. That is what we’re doing with vitamin D. It’s actually a very logical course of events for understanding the disease process and effectively treating disease — this is where we’re going in the future.”

“The past three decades have been a very exciting time in which many new imaging modalities, including MRI and CT, have been developed. Imaging is still accelerating in terms of what we can get from it, both in the degree of information and the decrease in invasiveness.

“In our own MRI work, we’ve recently been able to come up with new imaging methods that are 10 and 500 times more rapid. This doesn’t necessarily get the patient off the table faster, but it does allow us to obtain more images per second, with more details in the images. Like a technique, which we invented back in 1996, that is now a widely used and successful product, we hope to help make this highly accelerated method for blood vessel imaging commercially available.

“A related technique in X-ray CT allows us to decrease the radiation dose by a factor of 10. We conducted a human X-ray CT perfusion study that was taken with full x-ray doses, then we applied our technique using just one tenth of the dose, and we got the same results. Such technologies relate to imaging studies where we obtain a series of images — not a single snapshot image — and where we’ve found that in the past that there’s a lot of redundancy in the information we collect.

“The use of lower dose X-ray CT perfusion scans will be very relevant for stroke detection. It’s speculative, but I’m hopeful that the same kind of imaging will aid in the interpretation of CT-based coronary angiography.”

“When I think about the future, I think about something we call ‘sustainable chemistry.’ There is a desire amongst chemists to use environmentally friendly conditions to make materials (i.e., plastics, etc.) and medically important pharmaceuticals. This trend is already apparent; there is a push to get away from using agents that are hard to dispose of or pose environmental concerns. Organic solvents are used typically in manufacturing materials and drugs, and special conditions are needed to dispose of these solvents. There is a growing movement to develop reactions that can be done in water (or with no solvent at all).

“One exciting illustration of how organic solvents can be replaced is in the use of liquid carbon dioxide as solvent for dry cleaning. We all breathe out carbon dioxide, and it is produced when we burn fossil fuels. Chemists have recently discovered that when it is liquefied, carbon dioxide can be used in dry cleaning. This represents a sustainable process that eliminates the need for solvent disposal.

“This year’s Nobel Prize in Chemistry went to Drs. Chauvin, Schrock and Grubbs for their work in metathesis chemistry, which has now gained widespread use in research and industry. One of the biggest advantages of this chemistry is that it creates fewer byproducts and hazardous wastes; the idea is to generate chemical reactions with readily available compounds but minimal byproducts. It will take many small steps to make this happen, but it’s the direction we’re going in — I am confident we will make such strides.”

“On the horizon is the enabling tissue engineering technology that will allow the production of a variety of human tissues. Recent advances in the growth of cells without animal-derived products and the manufacture of certain types of human tissue using sterile, closed systems have positioned tissue engineering for rapid growth in the near future.

“In addition to therapeutic uses, engineered human tissues and organs could be used for genomic, proteomic, and imaging screens to identify new drugs and drug targets. It is exciting to consider the predictive power a systems biology approach to data analysis will generate using human tissue prototypes.

“Human cell sourcing is another facet of tissue engineering that will have long lasting impact on the practice of medicine and the development of new therapeutics in the future. Adult and embryonic stem cells hold such promise as therapies and will most certainly contribute to the discovery of novel therapeutics. The scientific process is critically important for identifying and harnessing the potential of these cells. The future is dependent on both science and society.”

“My hopes for the future tie in with my research endeavors here at UW-Madison and the desire to see real translation of stem cell research into therapies for human disease. My interests are in the diseases of myelin in the central nervous system, the material that insulates nerve fibers. We are trying to devise therapeutic strategies for both the genetic and acquired disorders of myelin, and I hope that similar approaches may work in both.

“MS is a disease that affects over 10,000 people in our state, with affected patients facing an uncertain future but with the likelihood of eventual progression to disability. While those with genetic disorders are many fewer in number, they usually experience severe neurologic disease and early death. We are seeking cells that could be isolated in sufficient numbers to repair the nervous system damage in these diseases.

“We are investigating the ability of a wide range of cell types, from embryonic stem cells to neural stem cells, to generate cells that can make myelin following their transplantation. I have great hopes that we will eventually generate sufficient myelinating cells from these types of cells. This is currently a major technological challenge. Once we get to that stage, we hope to be able to answer all the questions that the FDA requires be answered before we can actually use the cells in patients. And once these therapeutic cells can be generated, there is further work to be done to devise strategies that will allow delivery of the cells at various sites within the brain and spinal cord.

I do think this will happen — it’s just a question of time, effort, and technical know-how. I think we have to realize that progress is gradual and the research that will get us there happens in small increments and not continuous breakthroughs.”

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