Here is some exciting news from the Biotech world: The time is fast approaching when your personal DNA sequence will be readily available.
So what’s the big deal? Read on.
The human genome project
In 2003, the first complete genetic blueprint was published with great fanfare (President Bush, believe it or not, was present at the announcement). At the time, scientific pundits, journalists, and self-appointed crystal ball-gazers fell over each other proclaiming the benefits of this scientific feat. Indeed, the possibilities were, and still are, simply huge. People expected the advances to come tumbling down almost immediately; it did not happen. Why? Money! It cost about 3 billion dollars to complete the first sequencing in 2003. At that price, it would have cost about $900 billion to sequence everybody’s DNA in the U.S. Come to think of it, that’s not that much more than the Iraq war is costing us…
Fortunately, bright and competent people are engaged in this enterprise. The J. Craig Ventner Institute announced two months ago that it had completed the sequencing of, well, J. Craig Ventner’s genome. Cost: $60 million, or 2% of the cost of the original Human Genome Project’s DNA sequence.
Want more? There are now at least four companies that are racing to develop machines that will sequence a person’s genome for $10,000, or 0.017% of the cost for the Ventner sequence. In fact, the first one to reach the mark will win a $10 million prize offered by the X Prize Foundation. At this price, we could have everybody’s DNA sequenced for a total national cost of $3 billion—chump change, about 2 week’s worth of a dirty little war.
What’s the big deal about sequencing everybody’s DNA?
For this, you have to understand what DNA is made of. It is made of 4 chemicals, or bases, A, T, G, and C, strung together. Every three bases code for an amino acid, and those, strung together, make up the proteins that carry out all the functions that keep us alive and well. The sequence of these bases, and hence the sequence of the amino acids they code for, is highly variable. So, to be able to read the genomic blueprint, you have to determine the sequence in which they appear. The number of possible permutations in the order in which the bases, and amino acids, is arranged is essentially infinite.There are about 100 million bases in a chromosome, and there are 23 chromosomes—so you can appreciate the enormity of the task.
But you can appreciate another fact. No system is 100% error-free. As they say in Washington, mistakes have been made. The mistakes in the formation of the DNA, for instance, T instead of a G in a particular place, are actually quite common. They are called single nucleotide polymorphisms or SNP (pronounced “snips”, aka “point mutations”), and they are responsible for our individuality. This is why my daughter and son share a lot of traits with me and their mother, but are not identical to either one of us, and are not even “an average” between the two of us. They are truly unique. This is also the reason why the fear that people will clone their offspring, or the DNA of some famous people, in order to obtain a perfect replica, is misplaced—they will never get it thanks to SNPs (and thank God, or evolution, for that). The first and last individual to come close was Narcissus—and look what happened to him: He became something else—a flower (called narcissus). Not even close.
As part of our personality/individuality, SNPs determine something important: Our susceptibility to various diseases and our tolerance of different drugs. For instance, Ventner discovered from his DNA that he has a certain gene variant that increases his susceptibility to Alzheimer’s disease. Other variants are associated with cardiovascular disease, diabetes, basically all human diseases. Mind you, we are not saying that people with SNPs predisposing them to obesity will become obese. But they are predisposed to obesity, and most likely will have to work harder to ward it off.
Now you can begin to see the revolutionary importance of having a complete map of your DNA.
- You, and your physician, will know ahead of time what incipient diseases are lurking in the dark recesses of your genome. You can then take action. To avoid type 2 diabetes, you can control your diet. To avoid heart disease, you could adhere to a diet and exercise regime, get more frequent checkups, maybe even start on low dose aspirin as a preventative measure. The same goes for cancers, psychiatric disorders, etc, etc.
- Or consider this: We’ll be able to tell which child really suffers from ADHD or bipolar disorder, and who is just “being a kid”; no more fuzzy and subjective diagnoses, especially in psychiatry.
- We now know, from a field called pharmacogenomics, that people respond differently to different drugs. This, too, is controlled to a large extent by your SNPs. Some people take a drug called methotrexate for treatment of their cancer or rheumatoid arthritis and tolerate it without much of a problem. Others experience extreme fatigue, nausea, vomiting, anemia, infections, and other unpleasant side effects. The answer my friend is written in the SNPs.
- There are certain drugs that work in some people and not at all in others. One of those is a cancer drug called 5FU, another is the antiacid drug Zantac. I still remember that many years ago, the Japanese government refused to approve it in Japan unless the drug company conducted extensive clinical trials in Japan, because “the Japanese GI tract is different”. We attributed it to plain old protectionism. It turned out that many Japanese indeed react to the drug differently—because of a unique combination of SNPs.
- Psychiatric drugs are currently prescribed on a hit or miss basis. Some patients go through four or five drugs, different doses of each, combinations of drugs etc. until the desired effect is achieved. Why is this great variability? You guessed it. Knowing the patient’s genetic makeup ahead of time could avoid this terrible process of trial and error.
I could go on and on because the list is endless. But you get the idea.
The pharmaceutical industry
The business model of the drug industry depended on the discovery of blockbuster drugs, selling for billions of dollars a year. The industry is now changing its collective thinking. They realize that to make money, they don’t have to treat millions and millions of people; they could make it by focusing on a much smaller population, and deliver a drug that is essentially tailor-made for it. The upfront expense of clinical trials is enormous. The reason is that if the drug works on say, 50% of the people, you need many thousands of subjects enrolled in the trial in order to show a significant effect of the drug. But if you knew ahead of time the genetic makeup of the people who are likely to respond to the drug, then you’ll need only dozens, or a few hundred at most, to show the effect. The tremendous reduction in the cost of such a trial would make even a drug that is effective in only 10% of the population highly profitable.
This is not a theoretical model anymore, it actually happened. A small percentage of patients with chronic myelogenous leukemia (CML) have a certain constellation of SNPs in an enzyme that is central to the disease. The drug company, Novartis, decided to develop a drug that would be specific for these people. They saw it as a public service rather than a commercial undertaking. The drug, called Imatinib, was tested in the first phase of the trial in about 25-30 patients, to prove its safety. But lo and behold, it was also 100% effective. On this basis, the FDA quickly approved it. The company did not have to spend hundreds of millions of dollars and 15 years to bring it to market. This made it a very profitable drug.
The sociological effect
Without getting too deeply into the implications of these developments, here is a thought: We faithfully repeat the mantra that we are all unique individuals. Some truly believe in it, others (especially people in power) pay lip service to the concept, but in reality, expect everybody to behave the same. Just ask any teacher who has to deal with a bright, but restless, child. Or the police officer who has no time or patience for idiosyncratic behavior. Or the despot who brooks no dissent. But once the concept of uniqueness of the individual ceases to be just a philosophical idea and becomes rooted in our Biology, maybe, just maybe, we’ll learn to accept our fellow humans as uniquely individual, deserving of all the legitimacy and respect we’d accord to ourselves.
Now that would be a paradigm shift!