1．<International Circulation>: The technology of genomics has profoundly altered the conduct of medical research. The rapidity and scope of these changes in a research capacity have in turn led to speculation that medicine will be radically altered by the application of genomics to everyday practice. Could you tell us how long it will take us to cure disease or identify individual susceptibility with this technology?

《国际循环》：基因组学技术已经对医学研究产生了深远的改变，这些变化的速度和广度又会让我们推测，通过每天对这些技术的应用实践，生产的药物也将发生根本的改变。您能告诉我们，还需要多长时间我们才能利用这种技术治愈疾病和辨别个人易感性呢？

Prof. Marc Shelton: That’s a very good question. We have recently begun to accelerate our knowledge in the area of genomics， and there is increasing interest in the application of genomics to cardiology.  I think we are going to see in the very near future， meaning the next two to three years， the identification of genes and gene groups that are "high risk"， which may help us identify patients who need more aggressive therapy. Ultimately， it’s going to take a little longer in order to get more specific， gene-guided， choices of medicines. 

I think that this early period will be aimed at identifying high risk patients. Then， the next period will focus on strategies to reduce their risk， and ultimately， we may have an era in which there will be medicines targeted specifically to treat individual geneotypes. I think it’s going to take a while for the final step.  Furthermore， perhaps genotype-specific treatment will not be limited to only medicine. Perhaps we will find that some gene types are better off with specifically targeted diets. As you know， some people seem to eat lots of fat and get bodyweight， while others， if a different gene type， may eat lots of fat and get early plaque. 

In the future， some of the therapies maybe diet-modulated， some may require medicine， some may require interventional technology and stenting like we have seen this morning. It won’t be long before we will just draw blood on everyone， to check their genes as a matter of practice.

There are some new gene studies about blot clotting. Researchers are busy looking at patients who had stent thrombosis， to see if they have a genetic predisposition and those results will start coming out soon. 

Part of the difficulty with the current gene story is the fact that a lot of the events that are clinically important require the interactions of several genes. Not just one. So， for example， when we learned in biology that if you cross a white cow with a black cow， the result will be either a white calf or a black calf， we were learning simple Mendelian genetics there. It turns out that something like the genetics of blood clotting involves the interaction of several genes together. And so it’s a little harder to figure out if it was the black cow gene at work， or the white cow gene. For a protein to be effective， it may have to be in different forms or amounts， or in different interactions with other sites. So the genes are involved in several levels of very complex interactions. and the genetics of the human physiology are much more complicated than the simple genetics we learned in biology. 

Let’s see what else is interesting about that? Prevention may be an interesting part of the story.  For example， in the future we may be able to identify a genetic predisposition for having a heart attack at a young age. Will that patient be willing to quit smoking， follow a heart healthy diet and be compliant medicine? Perhaps if physicians are able to tell patients that they are at higher risk because of their genes， then the patients may be more cooperative.  Currently， in the US， and I think in other places too， the patients don’t always cooperate with our recommendations. 

For example， we have talked a lot about trying to get people to quit smoking， but you know it’s hard to quit smoking， so the patients have to be motivated.  Perhaps if we were able to say definitively to a patient: “You have gene X. That means your chance of having a heart attack at a young age is very high…”， then perhaps that could be an extra motivator for the patient to quit smoking. 

Right now， genetic screening is done mostly for research.  Part of the barrier to routine genetic testing is that it’s fairly expensive to do the test and not all insurances will cover it. So presently in the US， most studies are done as part of a research protocol that covers the cost of the test， and it hasn’t fallen into general use.  Over time， I think the cost of doing the test will come down and the test will become standard practice. . You know， we talked about the major milestones in cardiology: angiography， balloon， stenting， etc.. Genomics application in cardiology is going to be a major milestone， huge， ultimately. We will look back ten years from now and say the genomics story was one of the most important advances of the decade.

Marc Shelton教授：最近，基因组学领域的进展非常迅速。近年来，研究者们越来越热衷于基因组学研究以及将基因组学技术应用于心脏疾病。我认为，在不远的将来，也就是大概2～3年的时间，我们将会发现心脏疾病相关的某些基因或是多组基因。这些基因可能提示我们哪些患者需要更积极的治疗。最后，要达到更为特异性的治疗（即基因指导用药），还需要更长时间。我认为，早期基因组学研究是关于高危个体的检出。下一阶段的研究是如何降低患病风险，最后才是开发特定的治疗药物。因此我认为，距离最终目标的实现还有一段时间。同时，我认为基因组学研究并不完全是有关药物的研究。我们知道，某些基因型的个体适应不同饮食。有些患者摄入大量脂肪后体重增加，而另一些患者可能早期就有斑块形成。因此，一些治疗可能受饮食的调节。对某些患者需要给予药物治疗，而其他患者可能需要介入治疗和置入支架。未来我们只需采血分析基因型，仅用一小块基因芯片就能够做到。我们将很快实现这一目标。

目前开展了多项观察凝血相关基因的研究。我认为，研究者们正在积极观察支架置入后再次血栓形成的患者，目的是研究这些患者是否具有遗传易感性。很快就将得出试验结果。很多具有重要临床意义的事件都需要多个基因的相互作用，而不是单个基因在起作用，这就是基因研究的难点所在。我们曾经在生物课上学习到，如果一只白色奶牛和一只黑色奶牛交配，生出的小牛犊可能是黑色或白色的。这是非常简单的遗传学理论。但是，研究显示，凝血等过程涉及多个基因的相互作用。这比只有单一基因参与更难判断。蛋白质要发挥功能，就必须有多种不同的形式、不同水平或者与其作用部位发挥不同的相互作用。因此，基因参与多层次的相互作用，而不仅仅是一个层次。人体的情况比我们以往在生物课上所学的要复杂得多。另一件有意思的事情是，如果发现某位患者具有特定基因，我们就会认为该患者可能在早年就患上心脏疾病。那么这些患者是否愿意戒烟、按照食谱进食并且服用药物呢？为了预防发病，这些都是必须要做的。我们会告知患者，由于基因的缘故他会有很高的发病风险，患者有可能更愿意配合治疗。在美国，患者并不总是听从医生的建议，其他国家也存在此种现象。我们费了很多口舌让患者戒烟，大家知道戒烟很难成功。因此要用一些手段来激励患者。如果我们对患者讲，你的基因型意味着年轻时发生心脏疾病的风险很高，也许应该戒烟。患者可能就听医生的话了。

目前，基因组学还仅仅是停留在研究阶段。基因研究的问题之一就是研究花费高昂。随着研究的不断改进，我想基因检查的花费会逐渐下降。但是，目前费用还相当高，并不是所有保险公司都能够为此种检查付费。因此，目前某些研究是关于研究方案的，还没有得到广泛的