The Plant - Human Health Link

Summary

Recent advances in biological research have enabled Boyce Thompson scientists to study plants, insects, nematodes, and viruses at the molecular level, and to develop tools and techniques that have revealed new information about the workings of the human body as well. Key discoveries made at BTI may lead to novel ways to treat genetic disease and cancer in people, provide more natural blood pressure control, and deliver important nutrients in food.

Most people are aware that for thousands of years plants have been a primary resource for the treatment of human disease. In fact, three out of four people in the developing world continue to rely on remedies made directly from plants, and, in the developed world, a large percentage of prescription drugs contain at least one plant-derived compound. Most people are not aware, however, that the secret life of plants, insects and viruses can provide information directly applicable to human health. Today, thanks to molecular biology and biotechnology, BTI scientists are able to study basic life processes in plants and other organisms that can improve our understanding of similar processes in humans or can be used to deliver important new treatments. This is basic research with direct applications to human health.

The Issue:

Human medicine has made amazing advances, but some very significant hurdles remain to be overcome. How can genetic diseases be cured more safely through gene therapy? How can people who have limited access to medical assistance or can’t afford medications gain better health? How can science learn from stem cell research without using human tissue? How can we overcome the diseases associated with old age? And, how can the body’s own processes be used to treat disease?

BTI scientists are finding answers to these questions through basic research. We’re studying how some plants produce and store compounds that can prevent human disease and we’re transferring that ability into staple food crops. By investigating how nematodes regulate their life span, we’re learning how to control the rate of aging. By understanding how viruses enter insect cells and insert new DNA into those cells, we’re developing knowledge that one day may make human gene therapy safer and more effective. We’re also engaged in research to define the genetic cues that cause stem cells to become specialized cells in plants. Because these cues are similar in plants and humans, our findings may lead to new ways to treat currently intractable diseases, such as Parkinson’s or some forms of cancer, without the ethical issues involved in human stem cell research.

Plants, insects, viruses and nematodes – all under study at BTI – offer great potential for the further advancement of human medicine. A few of our research projects with direct applications to human health are summarized below.

Potential Impacts

The stem cell connection

All multi-cellular organisms, like plants and animals, have stem cells, and stem cells have the amazing capacity to become specialized cells. In plants, they might become flowers or roots or leaves. In humans, they might become skin or blood or muscle. What makes them amazing is that they remain stem cells until genes, working in concert, tell them to divide and differentiate into a special kind of tissue essential to the life of the organism. Being able to control when this happens and where it happens could be the key to curing diseases like cancer and Parkinson’s, repairing spinal cord injuries or muscle damage, or even regenerating whole, healthy organs to replace damaged ones.

In order to use stem cells for life-saving purposes, however, science needs to identify the genetic cues that trigger stem cells to divide and differentiate into specialized cells. Similar mechanisms regulate stem cells in both plants and animals, so understanding these cues in plants can advance knowledge about stem cell regulation in humans without the ethical issues that may be involved in human stem cell research.

To that end, BTI’s Ji-Young Lee, Ph.D., is investigating the genetic factors that cause plant stem cells in certain plant tissues to divide and generate xylem and phloem, which are the specialized vascular tissues that transport fluid and nutrients throughout the plant. Lee is studying this system in Arabidopsis, the “white mouse” of plant research. Using a high-throughput technique, she identified over 500 genes that may act in concert in Arabidopsis to generate xylem and phloem. Lee’s aim is to identify the function of these genes and how they work together in regulatory networks to cause the plant’s stem cells to become specialized xylem and phloem cells.

Understanding how these regulatory networks control cell specialization in one system in one kind of plant will reveal basic knowledge that is widely applicable. Lee’s research in Arabidopsis promises to shed new light on stem cell regulation that could lead to enhanced productivity in plants. Perhaps more important, this plant/human connection may generate knowledge that one day will be used to save lives.

The gift of sight…and life

According to the World Health Organization, 100 to 140 million children in developing countries suffer from Vitamin A deficiency. Each year, an estimated 250,000 to 500,000 of these children become blind, and half of them die within 12 months of losing their sight. If these children had access to foods with higher amounts of beta-carotene (the provitamin compound that the body turns into Vitamin A), this serious health issue could be alleviated or even eliminated. To that end, two BTI scientists are working on ways to provide people in developing countries with staple foods fortified with extra beta-carotene.

• Joyce Van Eck, Ph.D., developed two different ways to reach this goal in potatoes. In one research project, she silenced or “knocked out” a gene in potato that converts beta-carotene into a compound the body cannot use to make Vitamin A, theorizing that silencing the gene would cause the potatoes to accumulate more beta-carotene than conventional varieties. In other research, she inserted a gene from a high beta-carotene producing cauliflower into the potatoes, theorizing that the gene would cause the potatoes to produce extra amounts of the provitamin.
  Early results indicate that both approaches to the problem worked: Both lines of potatoes contained extra amounts of beta-carotene. Field trials will be the next step in Van Eck’s work to ensure that yield, plant health and other factors have not been adversely affected in the modified potatoes.
• Tom Brutnell, Ph.D., is focused on identifying lines of maize (corn) that naturally produce higher than normal amounts of beta-carotene for use in Africa and other developing countries where corn is a staple food crop. In his research, Brutnell described the process by which beta-carotene is produced in corn and recently identified a rare maize gene found only in high beta-carotene producing lines. Armed with this knowledge, Brutnell developed an easy-to-use toolkit for identifying the presence of this rare gene in corn germplasm.
  Using the kit, corn breeders in Africa will be able to easily identify the rare gene in North American corn germplasm and then cross that germplasm with lines especially adapted for African growing conditions. Brutnell’s kit is relatively inexpensive and promises to help African breeders generate local corn that provides the high beta-carotene content required to protect children from blindness and death caused by Vitamin A deficiency.

A new way to treat cancer

Cancer remains one of the most intractable of human diseases. For instance, there are about 186,000 new cases of prostate cancer each year in the United States alone, according to the American Cancer Society. Despite recent advances in treatment, more than 28,000 men die from the disease annually. For brain tumors, the statistics are even more troubling: About 22,000 new cases are discovered each year and, of those people afflicted, more than 13,000 die.

There is a new strategy for treating these and other cancers, however, which is based on insect virus research, and basic discoveries made at the Boyce Thompson Institute by Gary Blissard, Ph.D., and his laboratory team, may contribute to the development of the treatment. Blissard has been working to understand how certain viruses that infect insects invade cells and insert their DNA into the cell nucleus where they multiply and then exit. Interestingly, these viruses, called baculoviruses, can also enter mammalian cells, but they cannot multiply or cause disease in mammals – a feat with a limitation that makes them interesting as gene therapy vehicles.

Blissard has contributed to basic knowledge about baculoviruses through detailed studies of a protein in the virus’ envelope, called GP64. His team found that GP64 to the virus’ ability to attach to the host cell, penetrate the cell, and deposit its DNA into the cell nucleus. Understanding exactly how baculoviruses do their work in insects could help others refine a new technique for fighting cancer and other genetic disorders in humans.

The idea is to use the baculovirus’ natural abilities – and its limitations in mammalian cells – to advantage. Here’s how it would work: The baculovirus would be modified to include a therapeutic gene which the virus would deposit directly into the nucleus of the mammalian cell. Once inside the nucleus, the therapeutic gene would do its job: It might kill a cancer cell or even repair a cell defect. After accomplishing this mission, the baculovirus would die. Because baculoviruses cannot multiply or cause disease in human cells, this form of gene therapy may be safer than some others. Currently, researchers are testing baculovirus gene transfer systems for a variety of human diseases, such as prostate cancer and certain brain tumors.

In addition to human health applications, Blissard’s discoveries are important for agriculture. Baculoviruses are a natural enemy of insect pests, so a more thorough understanding of the virus’ infection process could lead to a more natural method of pest control – one that could reduce the use of chemical insecticides while it helps increase crop yields.

Lowering blood pressure, the natural way

Approximately one in three Americans has high blood pressure, which can cause strokes, congestive heart failure, heart attacks, kidney disease and other potentially fatal illnesses. Lifestyle changes, such as diet and exercise, can lower blood pressure, but when that doesn’t work, doctors prescribe prescription pharmaceuticals that can have a number of unpleasant side effects. But what if high blood pressure could be treated using the body’s natural control process?

High blood pressure results when there is too much salt in the bloodstream. Salt in the blood attracts water; the water raises the volume of blood, which, in turn, raises blood pressure. Normally, excess salt is drawn out of the blood by the kidneys and excreted in urine. If it were known exactly how the kidneys flush out salt, the result might be a new, more natural way to treat blood pressure.

BTI’s Frank Schroeder, Ph.D., studies this problem, among others. He developed a new approach for analyzing complex mixtures of small molecules, like urine, that uses nuclear magnetic resonance (NMR) spectroscopy – a powerful technique that helps scientists determine the chemical structure of unknown compounds. Applying his technique to partially purified rat urine, Schroeder identified three completely new small molecule compounds, or metabolites, in the mixture.

When these new compounds were produced in the lab and injected into rats, two of them raised the sodium level in the treated rats’ urine. Schroeder identified these compounds as members of a new class of hormones. Now, Schroeder’s team is studying whether these compounds directly influence blood pressure and what other functions they may have in the body.

It’s possible that Schroeder’s NMR technique will lead to an entirely new way to treat high blood pressure using naturally occurring small molecules he discovered. It’s certain that his new NMR technique will help identify other previously unknown small molecules in the body and help explain complicated bodily processes – research that could direct medicine toward more natural remedies for disease.