Winning iGEM, Building Companies -  Ingrid Swanson Pultz

最后，这种酶虽然容易制备，但有一些限制，让它没法大规模量产。

And then finally, this enzyme is easy to make, but it had some constraints that would prevent its manufacturing at commercial scale.

所以我们还得解决这个问题。

So we had to address that as well.

那时候我正好要从研究生毕业。

So I happened to be graduating from graduate school at that time.

我就跟大卫、贾斯汀坐下来商量，觉得这项技术太有前景了，不能像很多项目那样束之高阁、任其荒废。

And I sat down with David, with Justin, and we said that this technology is too promising to kind of just let it sit on the shelf ignored, which is what happens with a lot of these projects.

于是我就把它当成我在大卫实验室的博士后项目来推进。

So I took it up as my post doctoral project in David's lab.

那大概是2012年的事。

And that was in, yeah, 2012.

当时我还和贾斯汀、大卫一起创办了一家公司，叫Proteus Biologics，就是基于这项技术。

At that time, I also founded a company with Justin and David based on this technology called Proteus Biologics.

我的薪资经费来自现在的CoMotion——以前叫技术转化中心，是大学负责技术转让的办公室。

And I received funding for my salary from what is now CoMotion, and what used to be the Center for Commercialization, the university's tech transfer office.

我还拿到了一笔经费，用来雇了一位研究员和我一起干。

And I also got funding to hire a research scientist who worked with me.

这两笔钱都是用于技术转化的经费。

And those were both commercialization funding.

所以这个项目的初衷，就是帮我们渡过这个‘死亡之谷’。

So the intention of this project was to get through this valley of death.

我们能这么做，全靠CoMotion的支持。

So we had support from commotion to do so.

我觉得我们支持转化型研究，主要有两个原因。

I guess there were really two reasons we wanted to support translational work.

第一个是，我们希望在这里做的基础研究和设计工作，真能对现实世界产生影响。

The first was that we wanted our kind of basic research and design work here to have real world impact.

而要做到这一点，关键就是得跨过‘死亡之谷’，把化合物推到真正能走向市场、产生实际价值的阶段。

And for that, it was really important to cross the Valley Of Death to get our get the compounds to the point where they really could go out in the world and make a difference.

第二个原因是，这里有一大批顶尖人才，他们博士或博后一毕业，就特别想把自己做的东西真正用到现实中去，当个创业者，学会怎么把科研变成实际产品。

The second reason is that with all this incredible talent, talented people here who after finishing their PhDs or postdocs wanted to really have their really their heart set into becoming a really leading leading the charge to deploy the the things they've made in the real world and becoming an entrepreneur and learning how to do that.

通过这个转化项目，我们真正想解决这两个问题：资助那些研发出令人兴奋的新化合物的人，帮他们把成果推进到可以创办公司、真正面向实际应用的阶段。

And with the translational program, we really tried to solve both problems by sort of funding the people who developed the exciting new compounds to develop them to the point where they could start a company and really develop things for real world applications.

我觉得英格丽就是这个模式成功运作的绝佳例子。

I think Ingrid is just a spectacular example of how well that can work.

我问你个问题。

Let me ask you this.

把科研项目转化成实际应用，这事儿其实不新鲜。

So this idea of translating scientific projects is not new.

几十年来一直有人在做。

People have done this for decades.

但在贝克实验室里，以前有人这样干过吗？

But had it been done in the Baker Lab before in this way?

我们不是第一个从贝克团队孵化出来的蛋白公司。

So we are not the first protein company to spin out of the Baker Group.

之前已经有Arzada了。

There's Arzada.

亚历山大·赞加利尼在贝克实验室的时候创办了Arzada，但那时候蛋白质设计研究所还没成立。

Alexander Zangalini was in the Baker Lab and spun Arzada out, but that was before the Institute for Protein Design was a thing.

我们也不是第一个从IPD独立出来的公司。

And we were also not the first IPD spin out company.

第一个是Cyrus。

That was Cyrus.

Cyrus当初出来是为了让更多人用上Rosetta软件。

Cyrus spun out focused on increasing the accessibility of the Rosetta software.

他们主要是个软件公司。

They were predominantly a software company.

所以我们是第一个带着蛋白质资产从IPD独立出来的公司。

So we were the first IPD company that spun out with a protein asset.

KumaMax或者Kuma10酶这个项目，正好赶上了蛋白质设计研究所的成立，而研究所的核心理念之一，就是推动成果转化。

So this attempt around KumaMax or Kuma10 enzyme coincided with the creation of the Institute for Protein Design, and this idea that one of the things that this institute is all about is that translational work.

不只是做基础发现，还要帮这些发现成长，直到能变成公司、产品或者技术。

Not just the basic discoveries, but then helping those discoveries mature to the point where they become a company, they become a product or a technology.

是的，没错。

Yeah, yeah.

大概在2012年底，我开始在大卫的实验室做博士后，那时他刚搬进校园里新建的分子工程大楼。

In kind of late twenty twelve, I started my postdoc in David's lab, and he had just moved to the brand new molecular engineering building on campus.

那地方可真漂亮。

Very beautiful.

我在那儿特别开心。

I was very happy there.

兰斯是被大卫的实验室，或者医学院，总之是被聘来把蛋白质设计研究所真正搞起来的。

And Lance was hired by David's lab or the University of Medicine or something to basically make the Institute of Protein Design a thing.

在他的带领下，这个研究所很快就运转起来了。

And under his guidance, the Institute really got up and running.

他们启动了一个转化型研究员项目，专门给那些有商业化潜力项目的科研人员，申请后就能成为转化型研究员。

They started this translational investigator program, which was meant for scientists who were working on a project that was intended to be commercialized, could apply for and become a translational investigator.

这样他们就能自己申请经费，当自己项目的负责人，还能招人。

And that allowed them to get their own grants and to be the PI of their own project, to hire people.

我是第一个转化型研究员。

And I was the first translational investigator.

所以我帮兰斯一起把这项目搭了起来。

So I helped Lance put that program together.

几天后，尼尔·金也加入了，成了第二个转化型研究员。

And a few days later, Neil King was signed on as the second translational investigator.

后来，我们俩因为HHMI的规定，研究所决定把转化型研究员和其余团队物理隔开。

And then the two of us, because of HHMI rules, the Institute wanted to physically separate their translational investigators from the rest of the group.

于是我们去了J楼，专门腾出一片空间给转化型研究员用，花了好几天把那些老实验室里积了几十年的脏东西彻底清了一遍。

So we went to J Wing and set up that space for translational investigators, involved spending some days just scrubbing decades of filth off of some of the shells.

我希望这个转化型研究员项目能成为一条通道，让这里这些顶尖人才学会创业，创办成功的企业，真正把蛋白质设计推向现实应用。

What I hope the translational investigator program would become is really a route for these amazing people here to develop, to learn how to start companies and to start successful companies and, and, and, you know, really push protein design forward the sort of the applications to real world problems.

英格丽德就是这么走过来的，之后很多人都跟着她的路子走了。

That's exactly what Ingrid did, and that her path has been followed by by many since then.

从那以后，这个项目一直在不断壮大。

And the translational program is is has been growing ever since.

我们现在刚启动了三个新的转化项目，都特别让人期待。

And we just are starting three new translational projects, which are all very exciting.

从一开始到现在，这个项目已经壮大了很多，我真的很感谢Ingrid，不仅帮着把这事儿搭起来，还一直指导着下一代创业者。

So it's it's it's grown considerably over, you know, from the beginning, and I'm really grateful to, to Ingrid to both for, help putting it together and to help, you know, and for advising, the next generation of entrepreneurs.

Neil和我当初在J楼挨着开了实验室，我的团队一直很小。

So Neil and I both started our labs next to each other in J Wing, and mine stayed quite small.

就我一个人，加上研究科学家Clancy Wolfe，最多的时候也就再加两个人。

It was myself, my research scientist Clancy Wolfe, and then at the most we had two other people in the lab.

而Neil的团队却越扩越大。

And Neil's lab just grew and grew and grew.

所以我们后来得到了不少帮助。

And so we had help.

Frank DeMayo就在隔壁走廊有个计算机集群。

Frank DeMayo had a computer cluster right down the hall.

后来因为没地方了，我都被赶出实验室了。

And I was kicked out of the lab because there wasn't space for me.

所以我问他，能不能在他那儿放张桌子，待几周。

So I asked him if I could have a desk in his room for a couple weeks.

结果一待就是好几年，但他人真的特别好。

And then years later I was still there, but he's very nice.

他从来没赶我走。

He never kicked me out.

而且我还得到了大学外面很多人的帮助。

And so I had a ton of help from also outside the university.

我们特别依赖Comotion团队，他们提供了不少志愿者专家。

We relied heavily on Comotion to provide us with volunteer expertise.

我们有个很棒的企业家驻场导师，叫克雷格·菲利普斯。

We had a great entrepreneur in residence, Craig Phillips.

还有人帮我们搞生产制造方面的事儿。

We had people working with us about manufacturing.

也有专家帮我们设计动物实验。

We had people working with us about designing animal studies.

我们还请到了懂临床研究的人给我们提建议。

We had clinical people that could give us advice on clinical studies.

很多建议我们最后没照着做，但至少提前了解了这些将来项目肯定会遇到的事儿。

A lot of the advice we ended up not necessarily following, but it was exposure to these different things that were going to be coming down the pipeline for this project at some point.

所以我们得现在就开始琢磨这些事。

We needed to start thinking about it now.

于是我们就得自己出去找这方面的专家。

So, we had to go out and find that expertise.

好在大学的资源网挺广的。

But luckily, the university had a pretty good network.

我之前有没有提过转化健康科学研究所？

I don't know if I mentioned the Institute for Translational Health Sciences.

我们经常用他们那儿的服务。

We used them quite a bit.

华盛顿研究基金会也派了导师来帮我们处理这类问题。

The Washington Research Foundation provided mentors for that kind of thing.

我后来认识了一位华盛顿研究基金会的研究员，叫威尔·卡尼斯塔罗，他后来真的加入了WRF，在那儿干得特别出色，之后才离开，现在至少是兼职为一家IPD初创公司工作。

I actually got a Washington Research Foundation fellow, Will Cannistaro, who ended up actually joining the WRF and doing really great things there before leaving to, now he at least part time works for an IPD startup company.

但那时候他是我的WRF研究员，帮我跟兰斯一起做了一份净现值报告，这份报告把项目方方面面的因素都整合进去，帮你算清楚公司现在的估值是多少。

But at the time, he was my WRF fellow and he helped me to develop a net present value document with Lance that is basically a document that incorporates all kinds of different aspects of a project in order to help you calculate what your valuation is of your company today.

这玩意儿基于一大堆假设，还有各种风险测算，特别

So it's based on a ton of assumptions, and calculations of risk, and Very

这在商业圈里太常见了。

much a part of the business world.

没错。

Yes.

这事儿我读研的时候根本没人教过我。

Something that I was not trained for as a graduate student.

所以那段时间，我们在实验室里干了不少事。

So then, during this time, we accomplished a lot of things in the lab.

我们有个酶，看起来特别有希望。

We had this enzyme, it looked really promising.

我们得在真实场景里测试一下，看看它实际用起来怎么样。

We needed to start testing it in real world scenarios for how it might be used.

于是我们就去迪克的餐厅买了个汉堡和一杯奶昔，带回实验室。

So we went to Dick's and bought a hamburger, milkshake, brought it back to the lab.

其实我们买了好几份，给实验室大家都尝尝。

Actually brought several for the lab.

但具体操作是，我们把汉堡和香草奶昔搅碎，加了酶，再调成酸性，模拟人体胃里的环境，然后又加了这种酶，还加了一些当时正在临床试验、用来治疗乳糜泻的酶——但那些酶在胃里根本效果不好。

But specifically, we took a hamburger and a vanilla milkshake, blended it up, added the enzyme, acidified to represent human stomach, added the enzyme, as well as added some enzymes that were currently in clinical trials to treat celiac disease, but didn't work very well in conditions of the human stomach.

作为对照组，我们只用了面包屑加水，因为加奶昔和汉堡的目的，就是想看看这个酶在有其他蛋白质干扰的情况下还能不能正常工作。

And as a control, we used just the bun only and water, because the purpose of adding the milkshake and hamburger was to demonstrate, to see whether the enzyme can work in the presence of this other protein.

结果发现，那些天然酶在酸性环境下基本不管用，而且对麸质也没啥特异性。

And what we found was that it was a complete night and day response for these naturally occurring enzymes, don't work very well in acid, and are not specific for gluten.

它们确实能分解一部分麸质，面包里大概能分解个八九成，但一有其他蛋白质掺和，效率就掉到一半左右。

And so they broke down gluten to some level, it was maybe 80 ish, 90% for the bun, but only 50% if this other protein was present.

但我们的酶能达到99.9%的分解率，甚至在30分钟内就把汉堡和奶昔里的麸质降到了FDA认定的‘无麸质’水平，这真的太让人兴奋了。

But our enzyme was 99.9%, and in fact, it was degrading the hamburger and shake down to below levels that the FDA would consider gluten free in thirty And this was really, really exciting.

我们还拿啤酒试了试。

We also tried it in beer.

于是我们买了Chain Breaker的白IPA，这是一种小麦啤酒。

So we went out and bought Chain Breaker's White IPA, which is a wheat beer.

它的麸质含量比普通大麦啤酒高多了。

So it has a higher level of gluten than your standard barley based.

结果也是一样。

And we saw the same thing.

就算在冰箱里放着，十五分钟内，麸质含量就降到FDA认定的无麸质水平了。

And even at fridge temperature, within fifteen minutes, it was what the FDA would consider gluten free.

是的，我印象特别深，就是从那时候起，我们都觉得KumaMax真有可能成为一种药。

Yes, I remember very clearly, and that was the point where we all started believing that KumaMax could could really be a drug.

因为麸质消化前后的效果简直是天壤之别。

Because it was just really night and day before and after gluten digestion.

样品里的麸质基本被彻底清除了。

It pretty much cleared the gluten completely from the sample.

所以没错，那真是个让人激动的时刻，彻底让我们看到了酶设计在现实世界中的巨大潜力。

So yes, that was a very exciting moment, and it did absolutely bring home the potential real world impact of enzyme design.

我觉得这简直太

I think it's just such

完美地展示了如何把那些听起来特别抽象的实验室研究，和现实应用连接起来——毕竟实验室里都是在高度受控的环境下做测试。

a cool example of beginning to bridge that divide between what can feel like really abstract research that's happening in a lab where you're testing in a very controlled setting.

通常科学家做学术研究，都是买些纯化的分子，在精密的实验室条件下混合。

You know, normally the way a scientist would do academic research is you'd buy some purified molecules and mix them in in really precise laboratory conditions.

这么做是为了严谨。

And and that's for rigor.

因为这最终要发表论文，你得确保用的每一种分子都精确无误。

That's because this is gonna become published research, you wanna be really precise about all the molecules that you're using.

但像我们这个项目就完全不同了，这简直是绝佳的例子——当你想把研究推向真正的产品、真正的技术时，你就开始引入真实的东西，比如一个汉堡包。

But as a project like this, and this is just such a perfect example, as it tries to to move closer and closer to a real product, a real technology, you start to bring in things like a hamburger bun.

你开始真正地——

You start to really okay.

在实验室里，用纯化的分子、在理想条件下分解麸质，这是一回事。

It's one thing to break down gluten in a in a abstract laboratory setting with purified molecules under perfect conditions.

但要是把一个汉堡包、一口牛肉和一杯奶昔全混在一起，那感觉又会怎样？

But what is it like when you put a hamburger bun and and a bite of hamburger meat and a milkshake altogether?

这时候，这种分子还能不能正常工作？

Then how does the molecule perform?

如果它只在理想环境下有效，一到真实场景就失效，那这项技术就有问题了。

Because if it can't perform under those conditions, but maybe it only works in the ideal case, there's a problem with the technology.

所以你现在是在往真正吃汉堡的测试靠近了。

So you're moving closer to that real world bite of hamburger test.

是啊，我们就是想尽量还原真实场景。

Yeah, we were trying to make it as real world as we could.

对你来说，这种感觉是怎样的？

What did that feel like to you?

我很好奇，你以前可能习惯了那种实验室环境，现在却要把汉堡包扔进搅拌机里。

I'm curious as you, maybe you were trained in that one environment and now you're putting hamburger buns in a blender.

你觉得这跟以前有什么不一样吗？

Did that feel different to you?

太棒了！

It was awesome.

我们做这些实验特别开心。

We had so much fun with those experiments.

特别有意思，因为我们把真实世界的东西带进来了——我们去餐厅买了汉堡。

It was great because we're bringing in things from outside that We went to the restaurant.

我们买了汉堡。

We bought the hamburger.

然后把它带回了实验室。

We brought it to the lab.

我们加了酶。

We added the enzyme.

还加了一点酸。

We added a little acid.

然后我们把它混匀了。

And we mixed it up.

接着取了样品。

And we took samples.

我知道其实不是这么回事，但那时候真觉得我们是在把酶带进现实世界。

I know it wasn't, but it felt at that point that we were actually bringing the enzyme into the world.

因为我们是把整个世界带到了酶所在的环境里。

Because we were bringing the world into where the enzyme was.

没错。

Yeah.

转化型研究员项目在这段时期支持研究人员，但要想真正跨越死亡之谷，还得靠外部资金。

So the Translational Investigator Program supports its researchers through this time, but then in order to really bridge that valley of death, you need to bring in outside funding.

我们从生命科学发现基金拿到了二十五万美元，可惜这个基金现在已经没了。

We got $250,000 from the Life Science Discovery Fund, which unfortunately no longer exists.

但那是配套资金，另外还通过慈善捐赠匹配了二十五万美元。

But that was a matching grant, so it was matched by an additional $250,000 with philanthropy.

这让我们得以开展动物实验。

And that allowed us to do our animal studies.

所以我们用了普通的老鼠，给它们喂了面筋糊糊，再注射这种酶。

So for that, we used just normal rats, and fed them a gluten slurry, essentially, and gave them the enzyme.

半小时后，把动物处死，检测胃里残留的面筋含量。

And then half an hour later, the animals were sacrificed, the amount of gluten was quantified in the stomach.

结果三十分钟内，胃里的面筋就完全消失了。

And the gluten just disappeared in the stomach in thirty minutes.

这真是我们最关键的实验。

So that was really our pivotal experiment.

我们还用这笔钱做了一件特别重要的事——把生产环节从IPD独立出来。

We also used the funding to do something very important, which was to take the manufacturing out of the IPD.

当时，IPD里那个超强的生产核心正在建设中，由劳伦·卡特负责。

So at the time, the manufacturing core, which is an incredible asset at the IPD, was being developed, and it was being run by Lauren Carter.

她帮我们开发出了发酵生产的工艺。

And she helped develop a manufacturing process for fermentation.

所以我们在生物反应器里生产这种酶。

So producing the enzyme in a bioreactor.

然后我们把它带到一家制造工厂。

And we took it to a manufacturing facility.

这家工厂在爱荷华大学，他们有容量高达一千升的发酵罐。

This one was at the University of Iowa, where they have tanks that are up to 1,000 liters.

我们的目标是把技术转移过去，用标准化的方式大规模生产这种酶，这样才能满足后续研究的需求，最终向FDA提交申请，进入人体试验。

And the idea is that we would tech transfer and start being able to produce in a very standard way our enzyme in order to make the large quantities that are required to do the studies that are required to file an application to the FDA to go into people.

这其实也说明，这项工作正从传统的学术环境，慢慢走向实际应用。

So this is maybe another way where this work is moving from maybe a traditional academic environment more towards the real world.

你开始用上那些更接近企业级的生产工具和方法了。

You're beginning to use manufacturing tools, approaches that are a lot more like what you would see at company.

而且你这么做，就是为了拿到足够多的材料，去完成必要的测试。

And here, you're doing it to get the material you need to go through the testing you need to do.

但这一点

But it's

是的，能在大学期间就做到这一点，本身就很有说服力。

Yeah, and the fact that we could do this while still at the university was a big deal to be able to show.

要把这个项目从大学搬出去，我们能向潜在投资人展示，这个流程已经在工厂跑起来了，能生产出足够做研究的量。

To move this project out of the university, we were able to show potential investors that we had this process already running at a facility where they could manufacture enough that we could do these studies.

所以这对任何想投资这个项目的人来说都是个关键问题，毕竟产品能卖的价格是有限的。

So that is a huge question for anybody that's gonna invest in this project, because there's only so much you can charge for products.

你能不能把成本压到足够低，让卖这个价还能赚到钱？

So are you gonna be able to produce it at a cost that justifies making a profit and selling it at this much.

对，举个例子，假设你真搞出了个超级酶，吃下去能把汉堡包里的面筋全分解掉，变成无麸质的。

Right, so just making up numbers, it's maybe you do have an amazing enzyme, and maybe it really does turn the hamburger bun that you ate into basically a gluten free bun after you eat it.

但要是这一粒药要一千块，那顿汉堡套餐就变成一千块了。

But oh, if that costs $1,000 a pill, then you're talking about $1,000 hamburger meal.

这根本行不通。

That's kind of a nonstarter.

那简直完全没戏。

It would be a total nonstarter.

这些商业上的考量，开始变得和科学因素一样重要，甚至更重要。

Those business considerations start to become as important, maybe more important, than some of the scientific considerations.

这两方面你都得搞定。

You need to do all of them.

没错，就是这样，没错。

Yep, that's right, that's right.

当时我们把动物实验和生产流程都纳入数据包里，这真的特别有帮助。

Having this animal study and having this manufacturing process as part of our data package was really valuable.

那段时间，我尽可能多地去展示和介绍。

So during this time, presented as much as I could.

这让我认识了一位特别棒的导师——山田太奇，他早期就在IPD的顾问委员会里。

This led to meeting an amazing mentor, Tachi Yamada, who was on the advisory board of the IPD in its early days.

我都能专门做个播客讲讲他。

And I could do an entire podcast on him.

他真是个了不起的人。

He's an incredible individual.

可惜他几年前去世了。

Unfortunately, he passed away a few years ago.

Tachi 曾经主管盖茨基金会的研究部门，还当过葛兰素史克和武田制药的首席医学官和首席科学官。

Tachi used to run the Gates Foundation Research Division, and he was the CMO and CSO of GSK, GlaxoSmithKline, and Takeda.

圈子里没人不知道他。

Everybody knew who he was.

他一眼就看出了这项技术的潜力，主动提出要加入我们。

He really saw the promise of this technology and offered to come on board.

他还帮我们牵线，跟风投做了初步接洽。

He helped us sort of initiate preliminary meetings with venture capital.

那时候他看了我们的动物实验数据，直接跟我说：Ingrid，现在是该走了。

So at this time, he saw our animal data and said, Ingrid, now's the time to leave.

我却说：别急，我们还能再做点实验。

And I was like, No, more experiments.

我们真的可以继续做下去。

We can do this.

咱们可以看看这个。

We can look at this.

咱们能做成的。

We can do this.

咱们可以优化这个。

We can optimize for this.

他说，该走了。

And he said, It's time to leave.

这其实挺难的，作为学术研究者，总觉得自己还能再做更多实验。

Which is, I think, also a difficult thing where, as an academic researcher, there's always more experiments.

所以什么时候觉得成果够好了、该往前走了，有时候真得有人推你一把才行。

So knowing when something is good enough to move on, sometimes it takes that external kick in the pants to get going.

他让你走，具体是指什么？

So when he said leave, what did he mean by that?

他是说，把这项技术从学校里独立出来，成立公司，推向市场。

He meant spin it out of the university and into a company, and go into people.

天哪。

Wow.

所以我明白了，一个项目能不能成功，影响因素多着呢。

So learned that there are a lot of things that make a project succeed or fail.

当然了，如果科学上行不通，那肯定不行。

Of course, the science doesn't work.

但光有科学远远不够。

But there's so much more.

有没有哪种动物模型能提前预测这个会不会成功？

Is there an animal model that can tell you whether this will work or not, is predictive?

你能保护好知识产权吗？

Can you protect the IP?

你有自由实施的权利吗？

Do you have freedom to operate?

有没有别的专利可能会挡你的路？

Is there other IP that might block you?

这东西能量产吗？

Is it manufacturable?

我们刚才聊过了。

We talked about that.

成本能不能达到商业可行的水平？

Is it at a commercially viable cost of goods?

有没有毒性？

Is it toxic?

有没有什么限制性的毒性问题？

Is there any limiting toxicity?

给药方式或者剂量上有没有什么限制？

Are there any administration or dosing constraints?

在临床上能不能以合理成本验证效果？

Can you prove it in the clinic at any kind of reasonable cost?

你有没有一个能推着这事往前走的靠谱团队？

Do you have the right team to drive it forward?

还有监管障碍，有没有市场？

And then there's regulatory hurdles, and is there a market?

这个阶段的项目，要考虑的事情太多了。

And there's so much to consider about a project at this stage.

这些每一样，都是你之前说的那个‘死亡之谷’里毙掉项目的原因。

Each of those are what kills a project in that valley of death you were talking about.

每一条都可能致命。

Each one of those could be fatal.

没错。

That's right.

对，就是这样。

Yeah, exactly.

所以我们得把每一项都彻底调研清楚，才能让人信服，愿意投钱进来，推动项目前进。

So we had to really research every single one of those aspects in order to convince people that they should put money into this and to drive it forward.

我们原本是瞄准风险投资的，谈得还挺顺利。

We were originally targeting venture capital, and conversations were going smoothly.

后来有一段时间，我想应该是2015年吧，我之前提到的那些天然酶制剂，它们在真实世界中用于治疗乳糜泻患者的二期临床数据公布了，结果是阴性的。

And then at one point, I think this was twenty fifteen, are those naturally occurring enzymes in clinical trials that I'd mentioned, their phase two data in which they're using the enzymes to help people with celiac disease in a real world scenario came out, and it was negative.

也就是说，这些酶跟安慰剂比起来，并没有帮到患者。

So those enzymes did not help people, compared to placebo.

不过这里有个小注释：其实安慰剂组的患者反而有改善。

Now, the asterisk there is that people on placebo improved.

这其中的原因有很多，我本来可以细说，都是一些推测性的想法，但……

And there are a number of reasons for that I could go into that are hypotheses, but

安慰剂这东西真挺玄乎的。

Placebo's a strange thing.

但安慰剂效应确实是真实存在的。

But the placebo effect is real.

按理说，这个结果应该让人觉得更有希望才对，因为人们会想：哦，连安慰剂都有效，那这疗法岂不是更有潜力？

The result from that was that you would think that that would be helpful, because people would say, Oh, now this is even more promising.

可实际上，这反而让人们对用酶来治疗乳糜泻这个思路产生了恐惧。

It actually spooked people from the whole mechanism of using enzymes to treat celiac disease.

所以现在，风投都不回我们电话了。

So now, VCs were no longer returning our calls.

塔奇说：‘没关系，我们其实也不需要他们。’

And Tachi said, Well, we don't need them.

我们直接找药企就行了。

We'll just go right to the drug companies.

反正这东西最后也是他们来买。

Those are the people that would buy this anyways.

于是我们就找了所谓的战略合作伙伴，干脆绕过风投了。

And so we went to what's called strategic, so strategic partner, and bypassed VCs entirely.

那时候，我也得组建一个团队来干这事。

So at this point, I also had to build a team to do this work.

我接触过不少潜在的CEO人选，但要把自己一手带大的项目交出去，真不容易。

And I went through a lot of different potential CEOs, but it's hard to give your baby to someone.

之前所有CEO的事儿都是我亲力亲为，但我知道，这根本不是我想干一辈子的事。

You know, I've been doing all the CEO work up until this point, but I knew that wasn't what I wanted to do.

我想专心管科学部分，不想天天应付CEO那些琐碎杂事。

I wanted to be in charge of the scientific part of the program, and I didn't want to have to deal with all of the things that a CEO has to deal with day in, day out.

所以我打算组个团队，配个CEO、首席医学官兼首席开发官、生产人员之类的，还得有个实验室。

So my goal was to hire a team with a CEO, a chief medical officer slash chief development officer program, manufacturing people, etcetera, and also have a lab.

要把这么一帮人凑齐，真不容易。

So putting that team together was hard.

有位风投跟我们说，好团队能让平庸的产品成功，烂团队再好的产品也能搞砸。

We had a VC tell us that a great team can make even a mediocre product succeed, but that a mediocre team can fail even a great product.

所以很明显，他们投的其实是人。

So it was very clear that they invest in people.

关键是要找对人。

So getting the right people.

我觉得这在任何层面都成立。

And that's true at any level, I think.

你最宝贵的资产，就是那些真正在做项目的人。

The most important asset you have is the people that work on the project.

所以我们组建了团队。

So we built our team.

我们找了一支很棒的团队。

We got a great team.

我们最高峰的时候，PVP这边有九个人。

At our largest, we were nine people at PVP.

我们不得不把名字从Proteus改成PVP，因为当时我们一无所有，银行里只剩一千块，却收到了一家叫Proteus Digital Health的加州公司的律师函，要求我们停用这个名字。

We had to change our name to PVP from Proteus because we got a cease and desist letter from a California company called Proteus Digital Health, back when we had nothing, and we were just a company in name only with $1,000 in our bank account.

所以我们根本没能力跟他们打官司。

So we didn't have the means to fight it.

干脆就改了个冷门、绝对不可能撞名的名字。

So we just changed the name to something that was obscure and unlikely to infringe on anything.

PVP其实暗指西雅图的电子游戏文化。

PVP harkens to Seattle's video game roots.

我老公在游戏行业，PVP就是玩家对玩家的意思。

So my husband is in the video game industry, and PVP stands for player versus player.

还有这个叫Cumamax的酶，它本身是一种蛋白质，而我们针对的是麸质——也是一种蛋白质。

And Cumamax, the enzyme, is a protein, and we're targeting gluten, which is a protein.

所以是蛋白质跟蛋白质对抗。

So protein versus protein.

蛋白质对蛋白质。

Protein versus protein.

PVP这个名字就是这么来的。

And that was where the name PVP came from.

明白了。

All right.

PVP后来开始和武田制药接洽。

PVP started talking to Takeda Pharmaceuticals.

从我们最初跟武田接触，到最终敲定资助这笔研究的协议，整整花了一年时间。

It And took about a year from when we originally started talking to Takeda for the deal to get in place that would fund this work.

所以我们和武田制药达成了合作。

So we entered into a partnership deal with Takeda.

不知道你有没有听说过，武田制药是家总部在日本的大药企，对吧？

For those who don't know, Takeda's a large pharmaceutical company based in Japan, is that right?

是的，不过它在美国也有办事处。

Mhmm, but has offices in The US.

协议内容是，武田会资助这项研究直到一期临床试验结束，如果他们对结果满意，就有权以低于市场价的价格收购这家公司。

And the deal was that Takeda would fund this work through phase one clinical trials, and then if they were happy with the results, then they had the option to purchase the company at a price that was below what would be considered market price.

然后呢

And

如果他们决定不收购，这个项目资产就会回到PVP手上。

if they decided to not purchase the company, then the asset returned to PVP.

所以他们根本没占股份。

So they had no ownership.

明白了。

Okay.

这其实是个双赢的局面，因为跳过了风投这个中间环节，一旦他们收购我们，所有收益都会直接落到创始人、大学和IPD手里。

So it was really a win win situation, because by cutting out the VC middleman, if they acquired us, then all of those proceeds went to the founders, and to the university, and to the IPD.

如果他们没买，那我们也拿到了三千五百万美元的研发资金，全投在这个项目上了。

And then if they didn't, then we just got $35,000,000 of development money that was put into this project.

天哪。

Wow.

他们真是赌了你一把。

So they really took a bet on you.

是啊，他们确实赌了。

They did, yes.

太惊人了。

Wow.

所以我们当时面临一个特别棘手的分拆局面——得先跟大学把授权协议谈妥，不然没人会愿意投钱，毕竟你得有这项技术的独家授权才行。

So we had what I consider to be a difficult triangle of spin out, which is that we had to get the license in place from the university, because a company's not gonna put money into you unless you have the exclusive license to the technology.

所以我们有权利从大学那边获得这项技术的授权。

So we had the option to license the technology from the university.

公司那边也确实这么做了。

The company did.

如果你拿了授权，却还留在大学里孵化，这就构成利益冲突了。

If you have the license, and you're still incubating at the university, that's considered a conflict of interest.

所以我们得先拿到授权，才能融到资。

So we needed the license to get funded.

可要 spun out 才能拿授权，又得先有钱才能 spun out，简直是个死循环。

And we needed funding to spin out, but we had to be spun out in order to have the license.

所以这三件事互相卡着，形成了一个死结。

So it was a mutually exclusive triangle.

结果这三件事必须同时搞定。

So all of those things had to happen at the same time.

2016年12月那会儿，真是忙得脚不沾地。

It was a very busy December 2016.

但短短几周内，全给办成了。

But they all happened within a few weeks of each other.

之后我们就离开了 UW，搬进了 UW 旗下的孵化器——Fluke 大楼。

And then we left the UW, and we moved into an incubator space at the UW, we moved into Fluke Hall.

那时候团队有多大？

How big was the team at this point?

九个人。

This was nine.

我们在圣地亚哥有五个开发人员，在西雅图有四个实验室成员。

So we had a development team of five employees in San Diego, And we had a lab of four people in Seattle.

搬到新地方，那里叫Fluke Hall。

Moving to this new location, it's in a place called Fluke Hall.

感觉怎么样？

What did that feel like?

特别兴奋。

Well, it was very exciting.

我是说，我们真的从零开始建起了这个实验室。

I mean, we got to build up this lab from scratch.

我们确实是完全从零开始建起来的。

And we really did build it from scratch.

水槽都裂了。

The sink was cracked.

我们只好请人来修。

We had to have someone come in and repair it.

还得请电工来装两个四十伏的插座，给离心机和设备用。

We had to have an electrician come in and install two forty volt outlets for our centrifuges and equipment.

这完全是白手起家，就是为了把我们的宝贝项目搞起来。

It was building it from scratch, it was to carry out this, our baby.

你有没有哪一刻觉得紧张？

Was any part of it, were you nervous?

会不会觉得害怕？

Was it scary?

我紧张是因为不想让大家失望。

I was nervous because I didn't want to let people down.

对了，我记得你提到过，现在这项工作已经投入了三千五百万美元以上了。

Yeah, now there's, I think you mentioned, there's $35,000,000 and more invested in this work.

好几个致力于资助有前景科研项目的机构都给了你们资金，因为他们看到了你们这项技术，看到了你和团队展示的数据，觉得这真有希望。

Multiple groups that exist to fund promising scientific projects have given you money because they see this technology, they see the data you're presenting, you and your team, and they think there's real potential here.

我能想象，这肯定给你带来了巨大压力，肩上的担子很重。

I could imagine that creates a lot of pressure, a lot of weight on your shoulders.

是啊，压力确实很大。

Yeah, there was a lot of pressure.

这压力确实来自那方面。

And it did come from that.

但也不光是这个，我们做研究期间，好多乳糜泻患者给我们写信，问：‘这东西什么时候能用上？’

But it's not just that, because throughout our work, we had people with celiac disease writing us and saying, When is this gonna be available?

我太痛苦了。

I'm suffering.

我孩子也受罪。

My kid is suffering.

还有个波士顿的学生，自己办了义卖，把全部收入都寄给了我们，因为她也有乳糜泻。

We had people There was a student in Boston who had a bake sale and sent us all of her proceeds because she had celiac disease.

她觉得这事儿有希望。

She thought this was promising.

佛罗里达有个孩子每两周就把零花钱寄给我们。

Some kid in Florida was sending us his allowance every other week.

钱虽不多，帮不上大忙，但特别鼓舞人。

It doesn't make a huge dent in the ability to buy supplies, but it's motivating.

我绝不希望这项目因为人为失误而失败。

I did not want this to fail because of some person based mistake.

要是真得失败，也得是技术本身有问题，是我们没想到的。

If it's going to fail, it should fail because there's some issue with the technology that we couldn't predict.

没错，科学就是科学，现在你的任务就是带好团队。

Right, science is what it is, at this point, your job is to advance the best team.

对，我不希望因为我的疏忽，让这个项目黄了。

Yeah, I didn't want to have a mistake of mine be the reason that this project failed.

明白。

Right.

我猜那些义卖捐的钱，像你说的，对公司的运转可能没多大帮助，但对你个人来说，肯定特别有激励作用。

And I bet those bake sale allowances, like you said, it's probably not very important fuel for the company, but I imagine that's very important fuel for you.

是啊，确实如此。

Yeah, I'd say that's true.

它总让你想起自己为啥干这行。

Just reminds you what you're doing this for.

太了不起了。

Incredible.

接下来好几年，我们团队虽然只有九个人，但跟几十个顾问合作，有些人我们天天都得聊。

Yeah, so for the next several years then, there were nine of us, but we worked with a couple of dozen consultants, some of which we talked to every day.

所以我们有个庞大的顾问网络。

So we had a massive consultant network.

我们还跟很多CRO——合同研究组织——合作，把大量研发工作外包出去。

And we worked with a lot of CROs, contract research organizations, to get a lot of the work done, development work.

我们自己也在实验室里花了很多功夫，专注开发这一个项目。

We also did a lot in the lab developing this single asset.

我们改进了生产工艺。

We improved manufacturing.

从实验室的毫克级，一路做到一期临床的克级，再到二期的公斤级。

So we went from lab scale, milligram lab scale, to phase one scale, which was grams, to phase two scale, which was kilograms.

其实我们还得先生产出几公斤的原料，才能满足FDA要求、启动人体试验。

Although we actually did need to make a couple kilogram material to even do the studies that the FDA requires to go into people in the first place.

所以我们有了这套生产方法。

So, had this production method.

我们把Cumamax压成了药片，这事儿特别酷。

We pressed Cumamax into tablets, which was really cool.

还做了安慰剂药片，挺有意思的。

Made placebo tablets, which was fun.

最后我们顺利进入了一期临床。

We ended up going into phase one.

一期主要是看安全性和耐受性，这本来就是一期的核心目标。

And the phase one was safety and tolerability, which is what phase ones cover.

但我们还加了一个概念验证环节，让参与者喝了一杯含麸质的奶昔。

But we also included a proof of concept component wherein people ate a smoothie that has gluten in it.

大概半小时后，通过鼻胃管把他们胃里的内容物全部抽了出来。

And after about half an hour, all the contents of their stomach was sucked up through a nasogastric tube.

然后

And

接着测量了胃内容物中的麸质含量。

the content of gluten in that stomach content was measured.

就这么完了。

That was it.

这就是整个研究。

That was the study.

跟动物实验类似，但这次不用牺牲任何人。

It was similar to the animal study, but no one needed to be sacrificed.

我能问个随机的问题吗？

Can I ask a random question?

那种压制成片的纯化麸质降解酶药片长什么样？

What does a tablet of pressed purified gluten degrading enzyme look like?

这种情况下，药片还挺大的。

Well, in this case it was fairly large tablets.

研发过程中有个问题就是：怎么把药压成片？

Part of the development is how do you press a tablet?

我们希望药片尽量小，但剂量又要尽可能大。

And so that's as small as possible with as large a dose possible.

那时候这方面的研发还很少。

Not much development had gone into at this point.

确实挺大的。

It's fairly large.

看起来有点像那种浅棕色的膳食补充剂药丸之类的。

It looked kind of like a light brown dietary supplement pill or something.

但有意思的是，这些药片是我们2018年做的。

But it's funny because this was in 2018 that we made these tablets.

2011年参加iGEM的时候，有人拿了个药盒，把原标签撕了，贴了个叫‘Cumamax’的标签。

And in 2011, at iGEM, someone took a pill box, took the label out, and we made a label that said Cumamax.

就做个样子而已。

Just a mock up.

我们还弄了假的Cumamax药片，其实是紫色和黄色的M&M巧克力豆。

And we had fake Cumamax pills that were purple and yellow M and M's.

颜色更花哨一点。

Little more interesting colors.

从这个搞笑的点子，慢慢变成了真能装这种酶的药片。

So it went from that kind of funny concept to actual tablets containing this enzyme.

真在干活了。

Doing the thing.

你还记得当初你想象这些药片的时候吗？

Do you remember when you foresaw those tablets?

记得，我当时就想到了。

Yes, I did.

我记得。

I do.

那真是一段特别棒的经历。

That was a really cool experience, yeah.

我觉得这算是一个关键节点，毕竟你为这个项目投入了好几年。

I imagine that strikes me as one of those milestone moments where at this point you've put years into this project.

就像你说的，这可是你的孩子，是你亲手打造的成果。

Like you said, this is your baby, you're building this work.

我猜你天天想着它，连晚上都睡不着。

I imagine you're thinking about it night and day.

然后终于到了这么一个时刻——虽然这种节点不少，但这次不一样，这是有人真会吞下去的药片。

And then comes the point, there's many of these milestones, but that's a pill that a That person's gonna

有人会吃下去的。

a person's gonna take.

对，没错。

Yeah, that's right.

太惊人了。

Incredible.

第一阶段，我们做了这个实验。

So, the phase one, we did this experiment.

第一阶段我们设了几个不同组，测试了酶在不同条件下的使用效果。

We tested We had a few different arms in the phase one that looked at different conditions of how we would use the enzyme.

就像在大鼠身上看到的一样，我们在人体上也观察到了同样的结果。

And just like what we saw in the rats, we observed the same thing in humans.

在所有第一阶段的测试中，我们都发现 gluten 被大量分解了。

We saw a huge amount of gluten degradation in those phase one studies in every instance that we tested.

克兰西以前总说，这酶从不掉链子。

Clancy used to say that the enzyme does not like to fail.

所以，在所有这些不同组别里，这酶的表现都非常出色。

So we saw that the enzyme is doing very well in all these different arms.

只是人比动物要吵闹一点。

Except people are a little noisier than animals.

但有一个数据点很特别，有人服用了酶，结果酶没起作用。

And there was this one data point in which people had been given the enzyme, and the enzyme didn't work.

我们测出的麸质含量，跟安慰剂组一模一样。

And the amount of gluten that we pulled out was the same as placebo.

整个过程我们都是盲测的，数据进来的时候，我们根本不知道哪些样本含酶、哪些不含。

We were blinded through this process, and as the data was coming in, we were blinded as to whether the samples we were looking at had the enzyme or didn't.

顺便说一句，第一阶段用的全是液体酶。

And by the way, the phase one was done with entirely liquid.

药片是为第二阶段才压制成型的。

The tablets pressed in preparation for phase two.

这一阶段用的纯粹是液体酶。

This was just using liquid enzyme.

数据一出来，我们一眼就能看出哪些样本含酶、哪些不含，太明显了。

It was so obvious, as we were seeing the data come in, which samples had the enzyme and which didn't.

有的样本含麸质，有的不含。

Some of them have gluten, and some of them don't.

我们虽然盲测了，但其实根本没用。

That the fact that we were blinded did not matter.

但有个样本，他们用了酶，可残留的麸质含量跟安慰剂一模一样。

But we had this one sample where they got the enzyme, and they had the same amount of gluten as the placebo.

就这个样本，简直让我抓狂。

And that one just drove me nuts.

别人都说这数据太棒了。

Everyone else was like, This data is amazing.

干净得不可思议。

It's amazingly clean.

你瞧这个。

Look at this.

我指着的就是这个东西。

And I'm pointing at this one thing.

这到底怎么回事？

What happened here?

那这个又怎么说？

What about this?

作为科学家，你肯定会想：这些数据怎么该一模一样才对。

Because, as a scientist, you're like, This should all be the same.

在实验室里，条件控制得那么严，结果当然都一样。

And in the lab, your lab conditions are so controlled that it is all the same.

但人嘛，没那么整齐划一。

But humans are noisier.

所以我一直纳闷：这到底是怎么回事？

So I've always wondered, What happened?

是的，我们后来把这组数据发在了《胃肠病学杂志》上。

Yeah, so we published that data in the Journal of Gastroenterology.

然后在2020年2月25日，PVP被武田制药收购了。

And then on 02/25/2020, PVP was acquired by Takeda.

他们一看这数据不错，就直接收购了。

So they did like what they see and they acquired.

这时间简直太巧了，就在一切停摆前几周。

Which was incredible timing because it was a couple weeks before everything shut down.

我所有孩子的学校都停课了，是啊。

All my kids' schools shut down Yeah.

你之前问我，如果重来我会怎么做，我学到了什么教训。

For So you asked me earlier what I would do differently, what kind of lessons I learned.

我们最初的许可谈判费用高得吓人。

Our preliminary license negotiations were really expensive.

所以当我们谈技术许可期权的时候，必须通过律师事务所来操作。

So when we negotiated the license to option the technology, you have to do that through a law firm.

或者至少强烈建议通过律所来处理。

Or it's strongly recommended that it's done through a law firm.

你是大学员工，跟自己谈条件，这会被视为利益冲突。

You are a university employee, so it's considered to be conflict of interest to negotiate, quote, with yourself.

所以这事都得走律所。

So this is done through a law firm.

我们一开始找的律所不答应延期付款。

And our initial law firm didn't defer costs.

作为博士后，拿着那点薪水，付律师费真不是件容易事。

And as a postdoc, with the postdoc salary, it's not the easiest thing to pay legal fees.

后来我们就换了一家能延期收费的律所，这招挺对的——毕竟跟武田谈协议、签授权之前，我们律师费已经堆得老高了。

So instead, we moved to a law firm that did defer costs, which is good, because we racked up a huge legal bill in negotiating the agreement with Takeda, and the license, before we spun out.

他们答应等我们融到资再收钱，到时候一次性结清。

So they deferred their costs until we were funded, and then they got paid.

我明白了，明白了。

I see, I see.

我们最初把PVP注册成有限责任公司，当时觉得这事儿没啥大不了。

We initially funded PVP as an LLC, which we didn't think mattered.

但实际上，这对税务影响可不小。

But in fact, it does matter for tax reasons.

所以如果你从一开始就能注册成C型公司，税务上能省不少。

So if you can set it up as a C corp from the start, it's got a pretty big tax implication.

我们早期的股权结构本可以更谨慎一点。

We could've been a little more discriminating with our very early cap table.

当时请了几个朋友，给了他们比实际该给的多得多的股份。

We took on a couple of people at a higher percentage than we probably should have.

后来想招人的时候，发现手里就剩零点几 percent 了，想给新人一点激励都特别难。

And it becomes an issue later on when you're trying to hire people and you're just scrounging for a quarter or half a percent of a company to give to somebody.

这点对早期公司特别重要，得提前想清楚。

So that's, I think, something to keep in mind for early stage companies.

选CEO真的特别关键。

The choice of CEO is critical.

我们当时跟另一个人谈得挺深的，最后没选他，但他要是接手，公司现在可能完全是另一番模样。

We were in deep discussions with another person we ended up not going with who would've taken the company in a very different direction.

回头想想，其实早该拿点种子轮资金，毕竟团队里好些人长期拿不到工资，撑得挺辛苦的。

And then, in retrospect, we might've taken a little bit of money in seed money because some of the members of our team had to work at risk for longer than they were financially comfortable with.

所以，早点拿点种子钱，可能真是个明智的选择。

So, it might've been a good idea to take some seed money.

但最后一切都还好。

But everything ended up okay.

是的，后来武田收购了PVP，我就从PVP的全职首席科学官转型了。

Yeah, so then once Takeda was acquired, I kind of transitioned from being full time CSO of PVP.

PVP被武田收购后，因为疫情，我从全职首席科学官变成了全职在家教三个娃的妈妈，其中一个还是婴儿。

Once PVP was acquired by Takeda, I went from being full time CSO at PVP to, because of COVID, to full time homeschooling mom to my three little kids, one of which was a baby.

一个在上幼儿园，另一个在上小学预备班。

One was in preschool and the other was in kindergarten.

工作量一样多，但完全不一样，特别好的亲子时光。

And equal amounts of work, very different, really good bonding experience.

不过，那确实是我人生中一段挺特别的时期。

But yeah, that was an interesting stage in my life.

我记得你好像说过，让女儿们看到你做自己热爱的事很重要。

I think I've heard you say that it's important that your girls see you doing what you love.

我觉得确实很重要。

I think that is important.

这正是我做这份工作的原因之一。

That's one of the reasons why I do what I do.

你懂的。

You know?

我做这些，是因为我真心喜欢这个领域，也想让我的女儿们明白，长大后找一份工作、做自己喜欢的事，有多重要。

I do what I do because I love the subject matter and because, like, I want my girls to know how important it is to grow up and have a job and do something that you enjoy doing.

如果她们能看到我这样生活，或许也会觉得，这条路是值得考虑的。

So if they can see me doing that, then maybe they'll consider that as a legitimate life path for themselves.

不一定要当科学家——要是她们真进了这一行，我反而会又惊又喜，但总的来说，就是希望她们能有自己的方向。

Not necessarily being a scientist, would be shocked, pleasantly surprised if any one of them went into what I'm in, but just in general.

走自己的路。

Building their own way.

要不咱们聊聊当顾问这件事？

Maybe we could do this, an overview of working as an advisor.

是啊，PVP之后，我回到大学，跟他们说：这事儿我干过。

Yeah, so after PBP, I went back to the University of the Institute and said, I've done this before.

还有其他项目需要我帮忙翻译吗？

Is there other projects that I could help translate?

我在研究所做博士后的时候，有个一年级的研究生叫斯蒂芬妮·伯格，她正在用计算机从头设计一种微型结合剂，用来治疗IBD，就是针对IL-23受体的。

When I was a postdoc at the Institute, there was a graduate student, first year graduate student, Stephanie Berger, who was working on de novo, completely designed on the computer, mini binder to treat IBD, so an IL-twenty three receptor binder.

她想基于这项技术创办一家公司，找我帮忙起步。

And she wanted help founding a company spinning out based on that technology.

所以我帮她把这事办成了。

So I helped her do that.

这家公司叫Mopac Biologics。

And that company was called Mopac Biologics.

我在那儿干了五年，帮她把技术转化落地。

And I worked there for about five years, helping her to translate the technology.

这跟PBP完全不一样，同样有挑战，但也特别有意思。

That is a different experience than PVP, also very challenging, very fun.

那段时间，靠着启动资金，我们拿到了一堆特别棒的体内实验数据。

We got a lot of really awesome in vivo data during this time running on seed money.

最近，我又开始了一个新项目，合作的是贾斯汀实验室开发的技术。

And recently, I started a new endeavor working with a project that was developed actually in Justin's lab.

他现在在加州大学戴维斯分校。

He's now at UC Davis.

贾斯汀是那里的食品与健康创新研究所所长。

Justin is the director of the Innovation Institute for Food and Health there.

他的团队正在研发一种精准酶法脱咖啡因的技术。

And his lab is developing technology which is precision enzymatic decaffeination.

这跟之前的项目完全不一样。

So, very different project.

还是跟学生一起干。

Again, works with students.

现在还处于早期阶段，但特别有意思，理由也跟之前完全不同。

This is very early stage, exciting for very different reasons.

这次涉及的是FDA的食品板块，不是药品。

Also deals with the food component of the FDA, not the drug.

所以这是咖啡？

So this is a coffee?

这确实是一种咖啡产品。

This would be a coffee product, yep.

这也是用酶做的吗？

Is it also enzyme based?

对，是用酶处理的。

It is enzyme based, yeah.

之前是用酶去除面筋成分，现在这个是用酶来去除咖啡因。

So whereas before the focus was an enzyme that's taking out the components of gluten, this would be enzymes that help get rid of caffeine.

对啊。

Mhmm.

太厉害了。

Wow.

你刚才还提到和Stephanie的合作。

And then you mentioned this work with Stephanie.

我觉得在这两种情况下，你都是回到IPD或者找Justin——你可是联合创始人啊——提供你独特的视角，这真的很难得。

I think in both cases, they are instances where you returning, in this case, to the IPD or to Justin, you're a co founder there, and offering your perspective, which I think is really unique.

在这个蛋白质设计领域，或者 вообще 任何领域，能像你这样做的人都凤毛麟角。

There are not many people who have done what you've done in this field of protein design or really anywhere.

而且能做得好、做得成功，更是少之又少。

And to do that well and to do that successfully is exceedingly rare.

所以我很好奇，当你在早期阶段给科学家们提建议时，如果看到他们眼里闪着光，觉得这事值得干，你会看重什么？

And so I'm curious, when you think about the early stage advising on that work, if you're talking to scientists who maybe have that spark in their eye and they think that this is something they want to embark on, what do you look for?

或者你会给他们什么建议？

Or maybe what advice do you give?

毕竟你亲眼见过这事儿有多复杂、多烧钱。

Seeing what you've seen and how complicated it can be, how expensive it can be.

在最开始的阶段，你最看重哪些东西？

What do you look for in those earliest stages?

我觉得你得有这种心态：就算事情不顺，也不能轻易被打垮。

Well, think you have to have an attitude where you're not gonna get discouraged when things aren't going super great.

我觉得很多科学家其实早就经历过这些了。

I think a lot of scientists have that experience already.

而且你得明白，创业尤其是当你身居领导位置时，是会占满你所有精力的。

And I think that you have to recognize that starting up a company is, especially when you're in the leadership role, it is all consuming.

你没法再兼顾生活里的其他事了。

So you can do other things in your life.

那段时间我生了孩子。

I had kids during that time.

但你必须有来自身边人的支持。

But it's essential to have support, personal support.

我老公斯科特就特别支持我。

My husband, Scott, he's really supportive.

一天就那么点时间，你得学会安排和规划。

Also, there's only a certain number of hours in the day.

所以你得能高效地组织好自己的时间。

So you have to be able to organize and plan.

这活儿真不少。

It's a lot of work.

我很好奇，从你作为导师的视角来看，看着你带过的学生去自己创业、做点东西，是什么感觉？

I'm curious, from your vantage point as a mentor in all these different contexts, what's it like seeing people that you mentor go off and build things of their own?

太棒了。

It's so awesome.

这是我最喜欢的部分之一。

One of my favorite parts.

我们第一年的时候，我说过我们拿了iGEM最佳展示的亚军。

Our very first year, I mentioned we got runner-up best presentation at iGEM.

当时做展示的那个学生，也是我们iGEM团队的，叫Alec Nielsen，后来去了MIT，和Chris Voigt一起创办了Asimov这家公司。

The student that actually did the presentation, who was one of our iGEM students, Alec Nielsen, he ended up going to MIT and founding a company, Asimov, with Chris Voigt.

还有另一个学生，Chris Ivan，他创办了Gigacrop这家公司。

And we had another student, Chris Ivan, who founded a company called Gigacrop.

至于那个乳糜泻项目，真正干得最多的两个学生——其实我带过不少学生。

The two students that did probably most of the work on the celiac project, there were a number of students I worked on.

悉尼·戈登创办了一家公司，叫四十八生物，现在她在Zara工作。

Sydney Gordon founded a company called, I think it's called forty eight Bio, she's now at Zara.

还有莉兹·谢泼德，当时她叫莉兹·斯坦利，创办了诺维奥姆公司。

And Liz Shepherd, who was Liz Stanley at the time, founded a company called Noveom.

那是一家做微生物学的公司。

It's a microbiology based company.

还有杰夫，后来留在了校内的计算机科学与工程领域。

And then there's Jeff, who went into CSE here on campus.

罗什米是我们iGEM团队的学生，现在负责IPD的蛋白质生产核心团队。

Roshmi was one of our iGEM students, and she now runs the Protein Production Core at the IPD.

和这些学生一起做项目，真的能感受到他们的潜力，iGEM的经历让他们相信，自己也能做出改变人生的东西。

So just the talent and working with these students on their projects, I feel like working at iGEM really inspired them to get into the idea that they can build something that could be something that is life changing.

这真的太重要了。

And it's gotta be.

有太多人后来都走上了这条路，做出了类似的事情。

There's so many of them gone on to develop these types of things.

这真是一段特别棒的经历。

It's really been a cool experience.

我超喜欢和学生们一起工作。

I love working with students.

太棒了。

That's awesome.

我们现在正在录这一期节目。

So we're recording this episode.

我们俩都是华盛顿大学蛋白质设计研究所的成员。

We're both part of the Institute for Protein Design here at the University of Washington.

你在这儿待了这么久，肯定看到这里变化很大。

And you've really seen this place change a lot in your time here.

就连我在这儿的这段时间，它已经发展成一个相当庞大的体系了。

Even in my time, it's it's grown considerably into quite a machine.

而这个体系的核心目标之一，就是孵化初创公司，推动成果落地。

And and one of the things that the machine really is built for is is launching companies, is this translational work.