Princeton University - Council of Science & Technology

POPE PRIZE

Essay 1
The Unknowns of the Tropical Forest
Jon W. Benner

Essay 2
A Few Words about Spin one Half
Thomas S. Jackson

Essay 3
How Do You Grow Organic?
Ben Jones

Essays 4, 5 & 6
Competing against the Body
Irrationally Rational
Beyond the Genome
Laura A. Shackelton

Competing Against the Body
Published in the Daily Princetonian, Spring 2001, under this title

"I knew something serious had happened…I had been facing the left-hand side, preparing to hit a backhand, but turned because I had to retrieve the ball on the right side. It is a movement you do in squash all the time! But I turned one way and my knee totally gave out." Jen Shingleton '03 will never forget Princeton's second match of the 2000-2001 squash season. "As soon as I felt the pain, I collapsed."

Jen was forced to forfeit her match, but the trainer on-hand assured her everything was probably fine-she didn't hear an ominous popping sound and she could still manage a limp. Unfortunately, the following Monday, the news from her team doctor was not so promising. "Within two seconds Dr. Castello knew. I had torn my ACL." For Shingleton, this news was worse than the pain of the injury. She cringed at the words because she knew exactly what it meant. Too many of her friends had torn their anterior cruciate ligaments (ACLs.) A painful surgery, days of immobilization, and nine long months of rehab would lie ahead.

This story is becoming all too common among female collegiate athletes. Carrie Hughes, an athletic trainer at Princeton, says that out of 600 varsity female athletes, she sees about three torn ACLs every year. A recent NCAA report showed that the ACL injury rate for female soccer players was over two times higher than for the men (0.31 vs 0.13 occurrences per 1,000 athlete exposures.) In basketball, women were four times as likely to injure their ACL (0.29 vs 0.07.) The dramatic increase in the number of women and girls playing sports and the intensity at which they are playing has brought this issue to the attention of coaches and trainers. Women's sports were once played in a much slower, defensive style, whereas today women play with much more speed, precision, and power. With this, the overall increased injury rate in women has become apparent.

"It is amazing-all of the female athletes that have had this same injury," comments Shingleton. "The week after it happened people would ask me what happened and would say, 'Oh, I did that last year.' I feel it is like a right of passage for female athletes."

Three months out of surgery, Shingleton spends about two hours a day, along with the other members of her "ACL support group" (a collection of seven Princeton athletes all recovering from ACL surgery) doing rehabilitation exercises. Even with the great company, the process is still frustrating. "It's been three months and I still can't jog!-only a light stair master-nothing with high resistance. I am mostly working on strengthening my leg. You wouldn't believe how quickly it atrophies after surgery!" She is not only working to rebuild her hamstring, quadriceps, and calf muscle, but because the graft to replace the torn ACL was taken from the patella tendon, she will need to re-strengthen that region as well.

Besides the long hard months before her, Shingleton believes that one of the hardest parts about this type of injury is the psychological stress. " I am terrified I am going to tear the other one…I couldn't go through the surgery again-it was horrible. I know people become much less confident when they return to playing." Surgical repair of the torn ACL makes it less likely to tear than before. But what worries Shingleton and others is the fact that they are now more likely to tear their other ACL by overcompensating for the healed but weaker one.

There are at least three different theories explaining why females have a much higher risk of knee injuries than men. However, most trainers, like Hughes, believe it is a combination of all three factors that result in a high ACL injury rate. According to the hormonal theory, it is the surge in estrogen during a woman's menstrual cycle that loosens the ACL, a band that runs at an angle through the knee joint and connects the shin and the thighbones, making it easier to tear.

The second theory, the anatomical theory-which focuses on the female's narrower femoral notch, increased Q angle, and knee and foot dynamics-has generally been given the most attention. The femoral notch, which is the space at the bottom of the femur through which the ACL runs, is narrower in females. This can have a shearing effect on the ACL by the femur. Women also have much wider hips than men, causing them to have a greater Q angle. The Q angle is the measure of the angle between the quadriceps in the front of the thigh and the patellar tendon in the knee. A large Q angle naturally results in a greater angle between the femur and the tibia. This, in addition to a lower center of gravity, places extra pressure on the knee. Another result of a large Q angle is a more pronated foot-a further stress on the knee.

Unfortunately, these are things that are out of an athlete's control. So is there any hope, any way to reverse these painful trends? If the third theory, which has been gaining much more support in the last few years, correctly, or at least partially explains the rash of female injuries, then there is hope. According to this neuromuscular theory, women injure their knees more often than men because they use their leg muscles differently. Women's muscles are usually less balanced than men's. Their quadriceps muscles are much stronger than their hamstrings. These two muscles stabilize the ACL. When the powerful quadriceps pulls at the ACL, the weak hamstrings cannot resist and stabilize the knee joint.

Imbalances as these, however, can be controlled. Many doctors have devised special technique analysis and strength-training programs designed to identify and correct muscle imbalances. Although all of the programs differ slightly, most involve weights, stretching, and plyometrics to "re-train" female athletes. Many trainers have noted that women come to college with skills that are not "biomechanically sound." For example, among basketball players, females tend to jump and land with their legs straight. This puts forces four times one's body weight on the knee alone. Some are concerned that techniques like this result because female athletes do not receive the same quality of instruction as men do in high school. Whether this is the cause, or the problem stems from the fact that women naturally have different movements than men, no one can say for sure.

The question is whether it is too late to change these deleterious movements or if, by the collegiate level, they are ingrained too firmly in a player's form. "There are programs that teach the players how to jump and land," Hughes says, "but if they were started earlier it would help."

Techniques that train the athletes to become more aware of their body position should begin at a young age-high school at the latest. If training is begun early, then landing in a squat position when landing on two feet should become natural. When playing sports that require pivoting and cutting, a multiple-step stop would be second nature. (Whenever possible, athletes should avoid bringing their weight down on one foot in a single step.) And exercises that strengthen hamstrings, gluteus muscles, and the inner thighs would be routine.

One study, done by The American Journal of Sports Medicine, found that 80% of the knee injuries women incur could be prevented if athletes in high-risk sports, such as basketball, soccer, and volleyball, began these special training programs. Coaches and players are becoming more interested in these prevention programs now that they have been shown to work. There are clinics, videotapes, and books aimed at teaching the techniques and strength and flexibility exercises that can be used to avoid serious knee injuries. Hopefully the young, aspiring athletes will circumvent much of the pain and frustration Jen and thousands of other female athletes have endured.

Irrationally Rational?
Written in the spring of 2001

Do you believe humans are intrinsically rational? Princeton Psychology Professor Philip Johnson-Laird believes humans do not use logical methods of reasoning and he is ready to prove it. Test your ability at logical, rational thinking by contemplating this puzzle:

Only one of the following statements about a particular hand of cards is true:
There is a king in the hand, or an ace, or both.
There is a queen in the hand, or an ace, or both.
There is a jack in the hand, or a ten, or both.
Is it possible that there is an ace in the hand?

Subjects insist that the answer is yes, as Johnson-Laird predicts. But ask a formally programmed computer the same question and it will tell you that it is impossible to have an ace in the hand. If there is an ace, then the first two statements are true. But only one statement can be true. So an ace is not possible.

Johnson-Laird and his colleagues have created many of these illusions and the results are the same. Subjects consistently make systematic errors. If you were fooled by this illusion, don't despair. You are in good company. As Johnson-Laird explains, "there are vast differences in reasoning ability among different people, but even the smartest people in the world get these illusions wrong." Psychologists have generally believed that humans reason by using rational, logical rules. This is called the "formal rules" hypothesis. Of course, researchers have admitted, they often misapply the rules, but haphazardly. Using formal rules, reasoners should not make systematic errors. So why do almost all subjects succumb to the same illusions in the puzzles? Johnson-Laird believes he knows the answer. "Although we have the ability to use the 'formal rules' model, we usually do not." Instead, we reason by using assertions, things we know are true, to construct mental models of possible situations. His theory, called the "model theory" explains why certain inferences have conclusions, though incorrect, that are very compelling and drawn by most people.

When creating possible models of a situation in our minds, our working memory (the short-term memory that is used for math and reasoning) fills up very quickly. It runs out of room so we begin to leave out many possible models. We neglect to include critical information as in, "this picture is only true if the other picture is false." To save time and energy, our models almost always represent what is true, and not what is false. Given the statement "A or else B," we think about scenarios where A is true or B is true, not about the consequences of A being false or B being false. Most of the time this type of modeling serves us well. We have good reasoning abilities, and if we do make foolish mistakes on illusionary puzzles, we may feel ridiculous, but there are no serious consequences. Unfortunately, there are some fatal exceptions. Many are beginning to believe that this foolish reasoning has caused some of the most disastrous accidents we have known.

The engineers that were conducting the experiment which caused the Chernobyl meltdown knew the following two things:
"If the experiment is safe enough to continue, the turbines must be rotating fast enough."
And, "The turbines are not running fast enough."

The engineers should have realized that the first statement could be false and that the experiments were potentially dangerous. But they didn't-they continued operations, refusing to believe that something was wrong. They didn't believe the reactor had been destroyed even when they saw firemen in front of them holding graphite remains of the accident. Johnson-Laird believes this "refusal to accept facts staring you in the face" is a consequence of model reasoning. We don't model the possibly false situations. When suddenly faced with the false situation, we must entirely re-create our models. If we are under severe stress, our minds often freeze and we only use existing models. If we do not have an existing model of the current situation then we have no idea what to do. We cannot comprehend the false scenario because there is no model of it in our memory.

Many of these foolish mistakes in reasoning are caused by the simple pattern: "If A then B. If not B then what?" When asked to respond rapidly, most of Johnson-Laird's psychology students' immediate reaction was a mumbled, "Nothing?" However, given time we know that "if not B" it follows that "not A". Johnson-Laird believes that humans, when under stress or in a hurry often are confused by this simple logic. Johnson-Laird hypothesizes that this was the case in the 1983 crash of Korean Airlines flight 007. The pilot and crewmembers knew that if the plane was on course, they would see only water. But for almost half an hour they could see only a huge land mass. They did not come to the obvious conclusion that they had drifted over the Kamchatka Peninsula and into Soviet air space. They just continued-until a Soviet fighter plane struck them down.

Even when we are not stressed modeling falsity can be difficult. Most of us can easily identify potential falsity of simple clauses, but more complex false situations are different because they require extensive modeling. Johnson-Laird gives the following simple example:

If someone tells us that the statement, "Phil is in his office" is false, we all agree on its meaning. But if we are told the statement "Phil is in his office, Fred is in his office, and Frank is in his office" is false, most automatically assume that all men are not in their offices. They don't immediately take into account the many other scenarios which would also make the statement false-such as, "Phil and Fred are in their offices and Frank is not in his office." When the number of false scenarios becomes large, we simply leave them out of our mental models.

Johnson-Laird first proposed his model theory almost 20 years ago. Until then it was considered absurd to question the notion that the "laws of thought are the laws of logic." Now, more psychologists are accepting Johnson-Laird's theory as they explore human models and find how well they account for the systematic errors we make.

So how do errors in modeling affect us in our daily lives?

Our inexperience with modeling falsity may have something to do with our perception of risk. "Humans have difficulty coping with risk, numbers, and probability. We don't accurately model situations that involve doubt," says Johnson-Laird. This often causes us to grossly underestimate or exaggerate the probability that an event will occur-sometimes with horrific repercussions. Johnson-Laird believes that a gross underestimation of risk can be blamed for the rapid spread of AIDS in Africa. Similarly, an exaggeration of risk has resulted in the mass destruction of bioenginnered crops in Europe. One of Johnson-Laird's goals in studying mental models is to develop methods of informing people so they don't misconstrue probabilities in their mental models.

Our models also play a large role in many of our complicated emotions. Johnson-Laird's collaborator, Ruth Bryne, a researcher at Dublin University, is exploring how modeling falsity is related to the emotions guilt and regret. Our simple emotions provide us with a quick way of arriving at a solution. They are survival techniques that allow us to respond rapidly without wasting time reasoning. "Usually very rational decisions are made quickly as a result of emotions," says Johnson-Laird. But more complex emotions include both innate feelings and reasoning. To feel regret we must be sad about a situation that would have been different if we had acted differently. This requires us to model falsity. Do our problems modeling falsity cause us to be irrational about regret?

OK, you are probably wondering, why, if we are so bad at modeling falsity, can we comprehend fiction? Why don't we misconstrue novels? As we all know, a good author helps us create a realistic mental model of a fictitious atmosphere. But these fictitious models are modeling what is true, not what is false. As Johnson-Laird explains, "You enter the world of the novel and there are certain things that are true in the novel. It is true that Hamlet refrained from killing the king in Act II and didn't do it until Act IV." The case seems to be the same for dreams and daydreams. We model what we imagine to be true. So with all of this practice it is no wonder we are better at modeling assertions than negations. After all, as Johnson-Laird adds, with a smile, "it seems we spend more waking hours daydreaming than performing any other cognitive process."

Beyond the Genome
Will molecular biology's new focus-proteomics-revolutionize medicine?
written in the Spring of 2001 for a general audience

The red and green lights glare at you. Some are so intense they almost blind while others are faint and barely visible. You sit mesmerized, silent and still-a little scared but fascinated. It's so bizarre! What can those lights possibly signify? How can such simple bands of light hold so many secrets? But most importantly, what will they mean to your future, your health, and your children's health. You want to ask someone but for now you are transfixed by the detached and impassive hues glowing before you.

It is the year 2011 and, no, you are not sitting in your car dazed by the glare of a traffic signal. Instead, you are bent over a small but extremely powerful microscope, peering at your personal DNA. The bands of light define which of your genes are causing your cancer-what went "wrong" in your tumor cells. It's eerie being able to see so far into the roots of your illness by simply gazing at a slide of glass about the size of a quarter. But what's even more amazing is that these little lights provide the information that will guide your cancer treatment. You will not need to undergo the debilitating and unpredictable chemotherapy your grandparents and parents endured.

Is this possible? How can cancer treatment, which has lacked major innovation for decades, change so dramatically in the next ten years? Today, in 2001, many cancer patients are given routine therapies. The origin of a patient's malignancy is often a mystery and does not dictate treatment. In the most successful treatments, 50% of the patients respond somewhat, 25% do not respond at all, and 25% become sicker. How will we be able to change these bleak figures?

It all starts with the Human Genome Project that we have been hearing so much about. We were intrigued when the sequence was announced last summer-3.2 billion chemical letters spelled out. Some were somewhat less thrilled to find that this enormous genome of ours is the same size as the genome of corn and contains approximately 30,000 genes-a mere 50% more than the roundworm. Nevertheless, we accepted these footnotes and considered the Human Genome Project one of mankind's greatest scientific accomplishments.

WHY? This list of 3.2 billion A's, T's, C's, and G's is not much good in and of itself. The information was celebrated because it is the necessary starting point for what is to come. Genes are the cells' instruction manuals. They tell the cellular components how to make specific proteins. Each gene encodes different proteins. When scientists say they know a gene's function, they know the function of the gene's protein products. It's the proteins that carry out virtually every cellular process. Defective proteins cause genetic diseases. Drugs target proteins-not the genes that make them.

Sequencing the genome was the essential first step towards understanding the complex network of proteins. We think we have about 30,000 genes in our genome, but for the most part, we don't know the functions of their encoded proteins. Decades of research have resulted in extensive knowledge of only 4,000 genes-when they are "turned on," the appearance of the encoded proteins, and the roles of the proteins in our systems.

The 'post-genomic' era that we are now entering is referred to as functional genomics or proteomics. Ushering in this new age of research is Dr. Shirley Tilghman, a professor of molecular biology who, as a founder of Princeton's new Lewis-Sigler Institute for Integrative Genomics, was selected to be its first director. The institute is still under construction, but it looks as if Tilghman, who was also one of the founding members of the National Advisory Council of the Human Genome Project Initiative, will have to resign from her new post. On May 5^th, Princeton University announced that Tilghman, praised for her extraordinary vision and her commitment to education, was selected as the 19^th president of the University. But because of her excitement about the new proteomics project, she will undoubtedly continue to play a significant role in the program even as she leads the University.

As Tilghman explains, "giving meaningful labels to each gene" will be the Institute's first goal. She is not satisfied with current knowledge of gene function and research methods. The previous process of "researching one gene at a time is just too slow." Although the technology is not quite there, "the path is becoming clear how one experiment will be able to show the function of a lot of genes at one time." Once researchers accomplish this, Tilghman wants to focus on what she believes is biology's long-term goal. "The Institute is primarily designed to find and solve the next problem: how these proteins work together to form a complex system." Imagine if we could understand exactly how a cell senses its environment. Scientists have studied hundreds of individual proteins on cells' surfaces that take in information from their environment, other cells, and molecules. But as Tilghman contests, "we can no longer think about these one at a time. How does the cell compute and respond to all of this information?"

Integration and complexity-these will be the new buzzwords in biology. Focusing on the entire system will soon be possible. Scientists will finally be able to see how cells and their proteins work together and how these interactions are different in different people. We can only imagine how medicine will benefit from this new approach. Instead of treating illnesses broadly, doctors will be able to treat individual patients and their unique problems. Is it possible that medicine can advance this far in just ten short years? With the use of proteomics it seems very likely.

The collection of small lights seen under the microscope in 2011 is called a microarray. Doctors can already perform simple microarrays that tell them which genes are "on" in a particular cell-which genes are being used to make their encoded proteins. Almost every cell in our bodies contains all 30,000 genes, but only a few of the genes are active or "on" in each type of cell. When microarrays are used on cancer cells, they show which genes are overactive and which genes are repressed or "off" when they shouldn't be. This aberrant overactivity or underactivity of certain genes causes the cell to produce too many or too few of the genes' encoded proteins. The overproduction of a protein can cause the cell to grow uncontrollably-producing a tumor. Fortunately, drugs can sometimes stop these proteins and halt cell growth. Drugs work by binding to, or otherwise disrupting, the function of specific proteins in our bodies. The best drugs for curing diseases are those that are highly selective-they interfere with the functions of their target proteins while leaving the body's essential proteins alone.

Unfortunately, with diseases like cancer, the developed drugs are effective for only a handful of patients, and, more often than not, only partially effective. Even though most carcinogenic cells look similar under a microscope, their malignancy can be the result of mutations in, or the overactivity of, many different genes. Yet, today, the same drugs are used to treat the many different types of tumors. Doctors can attempt to choose which drugs might work best for a certain patient. But without knowing precisely which wayward proteins are causing the malignancy, they can only make educated guesses based upon undependable medical trends.

The first step towards improved cancer treatment will be to identify all of the possible genes that, when mutated or overactive, cause the cell to become malignant. Then, when microarrays are performed on the cancerous cell, doctors can know which overactive genes are causing it to grow uncontrollably.

Already, we can take genetic tests to see if we have the mutated, suppressed, or overactive genes that promote rare genetic diseases-cystic fibrosis, hemophilia, or Huntington's Disease. These are single-gene diseases resulting from the mutation of one specific gene. Scientists, however, know little about the myriad of genes that contribute to chronic diseases such as cancer, Alzheimer's, heart disease, hypertension, and asthma that affect far more people. It is difficult to predict which combination of mutated and overactive genes causes the disease-especially because the combination is different in every patient. There are hundreds of genes in the human genome that, when mutated, contribute to the likelihood of a person developing cancer. Each mutated gene will have a modest effect on the cell. Yet together, these small, cumulative distortions eventually produce the malignancy. Even though, "the methodology to study these diseases is still being worked out," Tilghman believes it won't be long until proteomics provides a detailed catalogue of all of the genes involved in complex chronic diseases-and, more importantly, their corresponding proteins.

Once we know all of the genes that can potentially cause a cell to become malignant, drugs can be created that target each of their overactive proteins. Proteomics centers such as the Lewis-Sigler Institute expect to create a database containing a description of every gene's proteins. Using the 4,000 proteins of known function and structure, computer scientists have been able to predict the function of proteins created by other genes. They have even been able to create three-dimensional dynamic representations of potential interaction with specific drugs. Scientists can find the best ways to interfere with the protein's harmful activities by testing virtual drugs on them. Currently this method is not as reliable as we'd like. It is extremely hard to predict the shape of a mature protein and how it will act in a given environment, even if the individual constituents of the protein, the amino acids, are known.

The Human Genome Project set off a frenzy of interest in cellular biology. Speaking three weeks ago at Princeton University about his role in sequencing the human genome, president of Celera Genomics, Craig Venter, stressed that from the genome will follow the proteins and from the proteins will follow genetic disease diagnosis and treatment. He is not the only one who believes that "over 90% of the interesting part of the genome has yet to be discovered."

In some cases biotech companies have been able to circumvent the issue of protein structure altogether in their eagerness to develop new drugs. Already they are creating drugs that attack specific carcinogenic proteins without having any clue as to what the target protein looks like. Their approach works in a few cases because the proteins they are targeting, cell receptors, are on the surfaces of the cells. Contacting and inhibiting these external proteins is much simpler than seeking out and inhibiting proteins working within the cell. Cell receptors have the job of sensing hormones and growth factors present in the cell's environment and relaying the message carried by these growth factors to the rest of the cell. In cancerous cells, these receptors are often overexpressed or mutated and tell the cell to grow and divide furiously even when there are few or no growth factors present.

The drugs that can shut down these dangerous receptors are actually antibodies-the same immune system particles that our bodies use to get rid of viruses and other undesirable intruders. Antibodies seek out the dangerous receptor protein-recognizing it by its specific shape-and then hold onto it so that it cannot carry out its harmful activity. If the protein is too large for antibodies alone to handle, they recruit larger components of the body's immune system. These components, with the help of the antibody, are now able to identify the receptor and destroy it. Because our own bodies cannot produce antibodies targeted against receptors on our own cells, mice and other animals in laboratories have done it for us. To generate antibodies, scientists isolate many copies of a dangerous receptor from human cancer cells and inject them into mice. Because the human receptor is foreign to them they raise antibodies against it. These antibodies are removed from the mice and, with a little tweaking, used as drugs for humans.

The developed drug must then go through rigorous trials before it may marketed. Scientists must be positive our bodies will accept them, that they will bind to the malignant receptors and not attach to normal cell receptors, killing our healthy cells.

When finally refined, genetic testing (using microarrays) on a patient's cancer cells will show which genes are overactive and causing the malignancy. Doctors can then administer a given drug only to cancer patients who have a specific overactive receptor. Patients will be administered drugs designed to attack their own particular defective receptors. They will no longer have to risk detrimental side effects of incorrect treatments.

There are already a few drugs available that can hone in on specific receptors. Genetech's drug Hersceptin that targets the HER-2 protein is an excellent example. HER-2 is a cell surface receptor present on most female breast cells. It responds to estrogen signals by dividing. In many cases of breast cancer, HER-2 receptors become overly sensitive to estrogen. The cell then divides at an increased rate. Genetech, armed with this knowledge, made antibodies in mice and "humanized" them so they could be given to patients in the form of the drug, Hersceptin. The antibodies are able to bind to and inactivate the HER-2 receptors in female breast tissue.

Although developments like this are encouraging, it is just a beginning. Cell surface receptors are only one of the many proteins responsible for making a cell malignant. Because many altered proteins, together, contribute to a cell's cancerous turn, more than just one errant protein will need to be arrested. Patients will need to be given a unique assortment of drugs-each designed to halt a single protein.

Even though our present microarrays will be helpful in diagnosing the combination of defective proteins, they are severely limited. As Tilghman says, "the information [current microarrays] give us is not the whole story." They can tell us which genes are overactive, such as HER-2. They can also tell us if an important gene, such as the famous tumor suppressor gene p53, is not working. Many times, however, a gene is mutated in such a way that the right amount of protein is made but there is something wrong with the finalized protein product. Perhaps the abnormal protein tells the cell to divide when no growth factors are present. Microarrays can only tell us how much protein is being produced, not if it is behaving properly.

It seems that the more we learn about cells and their functions, the more elusive they become. But biologists like Tilghman aren't frustrated by the new challenges and unforeseen complications they discover. The more complex the puzzle pieces nature throws at them, the more skilled biologists become at deciphering the puzzle's wonders. As the gaps are filled one piece at a time, the big picture is finally making sense and its intricacy, not its simplicity, is appreciated.

One notoriously gaping hole that is currently being filled provides an answer to the question of why two patients with identical forms of cancer, caused by the same combination of defective proteins, will respond differently to the same drugs. This can be partially explained by understanding the role of a particular group of proteins called membrane transporters which allow specific types of substances to enter a cell. If a cell has lots of membrane transporters that will accept a certain drug, then only a minimal amount of the drug is needed. Administering more than the minimal amount would cause an overreaction in the patient's cells. A patient could have a large number of the transporters because he has an extra gene encoding the transporter or because his transporter gene is especially active. Conversely, those patients whose genes for the transporter are missing, or inactivated, will not have any of these transporters to accept the drug. This patient will need to be given a large dose of the drug with the hope that a different transporter will allow it to enter the cell.

Once the genes that correspond to specific membrane transporters are identified, doctors will have yet another weapon with which to fight their patient's illness. They will be able to use microarrays to determine not only what type of drug to administer to a patient, but also the most effective dosage.

Computer scientists have already created virtual cells that can act like our cells. They soon will be able to "test" virtual drugs on these cells and monitor the cell's response. If this is successful, it is conceivable that personalized virtual cells and even personalized virtual immune systems will be created. The genetic data from an individual patient could be put into a program and a model of his cells and immune system constructed. After examining a patient's microarray, doctors could test the candidate drugs and drug combinations on the virtual models to measure their effectiveness, side effects, and the safest dosages. Imagine watching your body's reaction to a drug before you take it!

Even though many are experimenting with prototype weapons to fight cancer, an enormous amount of knowledge is still needed to fully develop these revolutionary treatments. Billions of dollars are being devoted to the burgeoning field of proteomics. Yet it is the number of great minds dedicated to the development of the field convinces Tilghman and Venter that it won't be long before we master novel and efficient ways of analyzing proteins and attacking some of our most devastating diseases.

The new proteomics programs are bringing together a diverse group of scientists eager to pioneer the new field. This is perhaps one of the first times in history that we will see molecular biologists, physicists, evolutionary biologists, mathematicians, chemists, computer scientists, physiologists, and geneticists collaborating their efforts to solve a particular problem. Tilghman believes "if biology had proposed this type of cooperation ten years ago it would have been a total waste. The time wasn't right." Biology has always been a data-limited science and unable to take this "whole-system" approach. But now that the genome has given us the data, the opportune moment has arrived. "A collaboration only succeeds when the planets are aligned and this doesn't happen very often." So keep your eyes open and gazing upwards because the phenomenon will be ours to view.