Giving an after dinner speech reminds me of a true story related by a Chairman in one of the departments I belong to. He was invited to be the after dinner speaker at a local medical society meeting.  He worked very hard, and he got his slides ready, went over to this medical society dinner, and they had the cocktails and the dinner, and he said, "Now?  Now do I talk?"  And they said, "No, not yet."  Then they had some more cocktails, and he said, "Now? Now?"  and they said, "Not yet."  So they went into the sauna of the hotel, and they all had saunas and steam baths, and everything, and he kept saying, "Now? Now?"  and they said, "No, no, not yet."  They got up to the after-dinner drinks, after they were back in sporty clothes, and they finally said, "Okay, you can give your talk now."  By this time, he said it was almost midnight, and everybody fell asleep.  So I'm hoping since we started earlier, that you will all be awake and able to listen to me. 

I'm also reminded of a speaker who was at a scientific meeting, who ended up his talk with sort of a smug query of, "Now, I wonder what I should call my new discovery?"  And a voice from the back of the room said, "Why don't you call it what I called it ten years ago, when I discovered it first?" 

The reason that I was reminded tonight of that last story is that, if Arthur Steinberg, who's now Professor Emeritus at Case Western Reserve University, Cleveland, Ohio, were here today at the symposia, or here tonight, I think what he would say is, "I advocated a lot of these guidelines for doing medical genetic studies on human populations in the 1950s."  And indeed, when I read a lot of the manuscripts that have been given us, and publications to go along with this symposium -- or workshop, as I guess it is treated -- I was struck by how many of the recommendations that many of you and other authors have put forth, were promoted by Steinberg used in the Hutterite studies beginning of the 1950’s.  For example, "People need to be treated not merely as subjects, but more as somewhat limited partners."  This was in one of the articles that was presented here by Greely. 

Really, the Steinberg philosophy, which we his students all learned as soon as we got into his graduate program, was very similar to that statement, and to other aspects that people have brought up today.  And the first and most important one, I think, was respect the culture.  As you will see a little while later, the Hutterites are somewhat of an old-fashioned communal population.  And simple things, like because the women wore long dresses, I wouldn't show up on a field trip in a miniskirt as I am in here tonight, for example.  We were very careful not to dress to insult them; we were careful to stay away from topics that would be offensive to them, and very careful to respect their cultural background.  

Second, get the cooperation of those in charge.  Steinberg found out in 1953, by doing a small pilot study on three colonies or communal farms, that the ministers in each colony called all the shots.  You could not go into a colony, do anything with the people, even talk to the people, without enlisting the minister's aid.  And that's exactly what he did, what I did later, and what people who are working in the population now do: check with the minister first, explain the research goals, explain what the study is about, explain how we plan to use the data, explain what data you want, and try to preserve the confidentiality and assure them of that.  

And I'll go a little bit later into -- well, actually I'll do it now.  The method we had of preserving confidentiality was to assign each individual study what we called a FINDIV number.  It was a five-digit, unique -- now I think it's a seven-digit -- number.  The advantage of this particular number was you could put it into a computer program written by Arthur Mange, later by others, that automatically constructed pedigrees, because of the way the numbers were selected, and also would print out all the longitudinal data back to the founder population back almost to the 1600s.  The other thing that this confidentiality number did is, you could, as you collected the medical genetic data, integrate it into this computer database.  Now, some of you listening here will say, "Well, that's not such a big deal."  But remember, this was in the 1950s, that this started.  I mean, today, it's somewhat easy, but in those days, Steinberg and his group were real pioneers.  The inbreeding program that Arthur Mange ran, after he coded the entire one population, as I recall, he told me it took one or two weeks to run in the computer.  When I was doing my founder study to find out, going back through all the pedigrees, who were the minimum ancestors of a the population, I had to hire graduate students to sleep in sleeping bags next to the computer, so that these long, involved pedigree searches could go on.  I mean, it's a far cry from what he have today.  So, you know, it sounds trivial, but in those days I think it was pretty progressive.

Some of the other things that Steinberg taught us, we have kept on for these studies, which is really forty years later.  The main study started in '58.  There were many of us involved Carole Ober at the University of Chicago is still conducting a lot of studies on asthma, on fertility, and in molecular biology.  So for forty years, we have kept up a very good relationship with this population.  

Now what's the payback for the population, which is another concern of this workshop? As I told some of you at our breakout session, it seems kind of trivial, but what the Hutterites liked in the ‘50s, and they still really like, is a printout of their family pedigree.  Now, it doesn't seem like a lot to us, but to them it's a big deal I checked with Carole Ober last week at dinner, and she said it's still a big deal; that's what they want.  They want their family pedigrees.  We also, in doing the blood pressure, cholesterol and medical checkups, provided them with any information that we found at the time, referred them to their local physicians if necessary, and gave them such information as blood pressure.  Now, we also had links with the local physicians.  I think this is very important, not only for follow-up with conditions you identify, but to alleviate any feeling from the local population that you're kind of sneaking in there and studying their people without getting an appropriate follow-up.  And it's useful for us.  One of the problems I had logistically, when I was going to the Canadian colonies one time is, we wanted to take a lot of our own syringes at that time, and needles, and we were taking specula to examine the women.  And so I showed up in the Canadian airport with a giant box full of syringes and needles -- very naive, right? -- and immediately was whisked into some room, where I spent about five hours while the rest of my team waited out there for me to be released.  So we were smart the next time: we got the local physicians to buy all the stuff for us, we sent them a check, that worked out fine.  So it's good to have local cooperation.  

We also promised the Hutterites, and this has been a promise we've kept, to only use the data for what it was we told them we were going to use it in the first place.  And of course, this has been updated over the years.  Now, that has caused some logistic and political problems for me, and I understand, for Carole, and I know for Dr. Steinberg. People will call you up and they'll say, "Gee, Alice, could you give me all the population blood pressures and inbreeding coefficients, and anthropometric data on your population, the Hutterites?"  And we usually say “no,” because the Hutterites didn't approve whatever it is these others want to do with the data, plus we can't be sure the other investigators are going to follow the same guidelines we did, in trying to publish this appropriately, keeping our pact with the Hutterites.  But as you can imagine, colleagues sometimes get very nasty and accuse you of hoarding data.  J.V. Neal, University of Michigan tole me when I complained about a fellow colleague that he knew who was badgering me mercilessly to get what I collected, said, "Well, he was always like that, and he never wanted to collect his own data." And also, the few times we have collaborated with people, it's after we're sure that the goals are consistent with the philosophy and the information we gave the Hutterites in the first place.  

Now, in reading again some of these workshop papers, as someone mentioned today there was nothing about the Iceland study in here, and I agree -- I was kind of surprised at that myself; I actually wanted to hear a little bit about it.  But the Iceland study and the Hutterite study appear to have certain similarities in terms of populations that are identified by scientists. We talked a lot today about who should identify these populations, but in Iceland there is a local company who has made a pact with a larger company, I think it's Hoffman LaRoche.  This was debated through the legislature, who noted, as I understand it, to go ahead with a genetic study, collecting DNA.  The reason the Icelandic population was of interest is because of its homogeneity.  One reason the Hutterites were of interest to Dr. Steinberg is they are relatively homogenous.  The Hutterites are a genetically inbred isolate that live in relatively uniform environments, and were ideal for medical anthropometric studies.  And why is that?  Well, someone asked today, "Why do we need to present the background of the population in a publication, or their genetic background?  Why can't we just present the data we've collected?"  Well, the geneticists in the room -- and many of the anthropologists who are sort of pseudo-geneticists, right? -- know that the phenotype, or the thing you're studying... Let's say you're studying heart disease or whatever.  You know that that phenotype is not based, usually, on expression of one gene.  It's usually the interaction of a gene or many genes against another genetic background.  Those who have done a lot of laboratory studies know a gene in one genetic background does not necessarily have the same effect as in another genetic background.  So genetic background is important, and the environment is important.  You put the same gene in a couple of different environments, you will likely get different effects.  And the reason, therefore, it's important to know where your population is coming from, that's why I don't think we can just do random studies, is if you publish a result, and you don't tell me what was the other genetic background, what was the environment these people lived in, I can't really evaluate if I can extrapolate that to a population I'm trying to provide genetic counseling for, or to some mechanism of a gene.  Now obviously, if you get really to some basic mechanisms, you may be able to say this gene does that, and you don't need background.  But in general, you need a lot of background there for understanding the genetics.  

In terms of anonymity, Dr. Steinberg tried initially, futilely, to say that he was going to hide the identity of the population he was studying.  Instead of them calling the Hutterites in his early work -- in fact, if you pick up two of the reprints I left on the table, you'll see this -- he called them the "H-Leut.  Leut means "people," and indeed the Hutterites call themselves “Leut,” but H Leut was supposed to disguise the fact he was studying the Hutterites.  Now, you know, and I know, that that's really a futile sort of protection.  The reason Dr. Steinberg was worried, and we still are worried, is that the Hutterites were a pacifist group that, as you will see in a bit, came from Germanic-speaking people.  During the World War, they were pacifists, and they spoke German; you can imagine how popular they were.  A couple of their young men were imprisoned in Leavenworth, and this would be around 1909, 1910, and two of them died in prison.  And there's a strong suspicion on the part of the Hutterites that they were tortured to death.  What happened as a result was that the Hutterites picked up their colonies, which then were mostly in South Dakota, and they moved all the colony people to Canada.  This is the reason for a big migration to Canada around that time, around 1910 to 1918.  They left a skeleton crew, really, of the older people back in their U.S. colonies.  Also, Hutterites are not a population that's universally popular with their neighbors; they're rich farmers, so the farmers around them are sometimes a little jealous.  

So this is a group, I think, that fits the kind of thing you're all worried about today, a population where maybe publishing some genetic studies, might make them more unpopular than they were already.  I can't see that this has happened to the Hutterites; I have asked some of the other people working with them, and we can't really see that there has been any effect, other than the problems they already had, from the studies we've published.  But that may be that there really aren't, how would you say, deleterious effects of genes that have come out of this study.  We showed inbreeding did not have a strong effect; we showed they're a fairly intelligent population; we showed they had a low cancer risk.   Carole is now showing that the fertility problems in the Hutterites are not more than the general population; it's just that she's pinpointing these fertility problems, early missed abortions, to HLA compatibility.  Where the parents are HLA-compatible, they will have a greater chance of having very early miscarriages.  So I think one reason maybe there hasn’t been a deleterious effect of research and publications is we really haven't said anything bad about them.  This may not work for all populations. 

A little bit about the background of the Hutterites.  They were founded in 1528 (it's a religious Anabaptist sect), and they migrated in a series of migrations, sort of picking up and losing people, until they ended up around the 1700s in Russia.  It was from Russia that they migrated to the United States, between 1874 to 1877, to escape, again, military conscription, and also to preserve control of the education of their children on the colonies.  When they came to the US, they formed three separate colonies, which again, Dr. Steinberg tried to hide the identity of by calling them S-Leut, L-Leut, and D-Leut, which actually are Schmiedenleut or Blackmith's People, Lehrer-leut, or Teacher's People, and Darius-leut, or Darius' People!  

Now, you talk about the internal politics.  We found out very quickly that, for reasons that I think are still not known, the Darius-leut were not as well thought of by the other two groups.  They were thought of as, you know, not quite good Hutterites.  The Lehrer-leut are very, very religiously strict; the Schnieden-leut are the group that have been most cooperative, and Dr. Ober tells me, are continuing to be the most cooperative.  So even within a group that originated from the same major group, you have political and personal differences.  And we've been very concerned about those.  There's a lot more colonies now; this is an old population.  What happens is, when a colony gets to a certain size, they elect a new minister, and they split - they buy new land, and as soon as that land is self-sufficient, half the group, approximately, moves to the new land with the new minister.  So there's kind of a binary fission.  

Over time colonies split and formed various colonies, and go on from there.  The colonies vary a lot in construction.  Some of the older colonies in South Dakota are fairly primitive; some of the newer ones are really quite fancy.  And their farming methods are quite modern.  One of the amusing things that happened to me is we got to one of the older colonies one time, and I asked one of the women, who seemed to be in charge, where the bathrooms were.  And she literally did this: she went [gesture] "The pigs have running water!  The pigs have showers!  The pigs have this!"  and she's pounding this table and berating the pigs, and she said, "And we have outhouses!  The outhouse is over there by the tree!"  Now, we noticed a few years later, we came back to that colony, they had inside plumbing.  I think she had her way.

In the past, Hutterite were totally served by a communal kitchen, and ate in a communal dining room.  All the women ate together, the men ate together, and the minister had his own table.  Now, I have to tell you ladies in the audience that when I went out there with my teams, which were mostly males, they just loved it when they put me at the women's table!  They thought that was very appropriate.  Now, the implication of this for Steinberg's original idea, was that you have a group with known pedigrees eating food from a common kitchen.  So if you're, for example, studying obesity, you don't have the problem where, okay, this family's fat, but Mother's cooking everything in bacon grease; this family's kind of trim, but they're all eating veggies all the time.  Here, they really don't sit with their family units, so they weren't seeing each other eat.  Children weren't watching Mom and Dad, and they were eating the same kind of food.  It's was very heavy Germanic food in the past.  There have been some changes.  Now, they're having more and more of their snacks, as they call them, in their own homes.  They all are starting to put kitchens in their new homes.  So they are changing; it's a population that probably is losing a lot of the characteristics that made them very good to study.  But this is the past situation.  

Hutterites really do have quite good food.  Although they're also diverging now, where some colonies are getting "health conscious."  So some of the cooks, there's a master cook who determines the menu for the colony, some of the women are now going into more of the heart healthy things, whereas other ones are still cooking with goose grease.  So it would be interesting if anyone -- we're not doing that now, but if anyone would ever go back and try to see the effects of the changing diet on these people, it would be rather interesting.  

They're certainly very, very good craftsmen.  Their places are quite comfortable.  Now, those interested in marriage patterns, I wasn't going to say much about this, but we found out that what seemed to happen is there are a lot of marriages, more than random, between two sets of siblings.  Now, they avoid close inbreeding, but we found that a whole bunch of brothers would marry a whole bunch of sisters, and I don't know if they're still doing it, but what they used to do is -- they'd have a barn painting, and so they would deliberately have all the young men and young women come from one colony to the other, so you would tend to have families meet each other.  Since many are all approximately around the same marriage age, you'd have a whole bunch of them suddenly marry another bunch from the other sibship.  So it was kind of an odd marriage pattern.  The women move with the husbands, so if the colony splits, the husband goes along with his family, and the women go along.  So you've got a lot more migration of the women around colonies.  

The other thing that Steinberg found that was really good about the Hutterites for genetic investigation was that they had large families.  The average family size, I think when he started, was about ten, and a lot of the estimates were that women were either pregnant or lactating for every year from marriage to menopause.  Now they tended to marry a little late, which is what saved them a bit, and when I was still out there, my last trip to the Hutterites was in 1982, by that time they were already starting to use any excuse they could for a hysterectomy, which is one way of shortening their reproductive period.  Carole Ober now tells me that they're moving toward use of actual birth control methods.  They need permission from the minister, and they aren't bragging about it, but their family sizes are starting to go down a bit.  They're still averaging five or six children, however.  So they're still big families.  So again, those familiar with laboratory studies, you know, you like your mice, you have a whole big sibship, showing genetic segregation; well, the Hutterites are pretty close to that in terms of human populations.  And there's almost no non-paternity that we could detect with all the blood groups, it is very, very rare.  So Hutterites are an extremely moral, monogamous society.

The colonies are located all through Canada and down here in the Dakotas, and a few scattered around.  Hutterites are actually very humorous too: I have not lived with the Amish, maybe some of you have, but the Hutterites are quite funny.  One the physicians that I took out there that asked why one Hutterite wasn't married yet, actually because the mother of the guy, when he went in to see the doctor said, "Ask Mike why he is not married!"  So this doctor asked, and the guy said to him, "Why milk the cow when you can get it through the fence?"  Now we don't know exactly what that meant, but...  They have designated jobs on the colonies.  We always knew when the pig man walked in for blood drawing.  The pig man had an arresting odor.

So again, the reasons Steinberg picked this population out for studies included a small number of founders, which is what I did my thesis on; high fertility; communal lifestyle. The family size when they started was quite high, and differed in the two groups studied (S-leut and L-leut).  They had an older age at marriage, they prohibited contraception, prohibited premarital sex, (and really when you're out there, it would be really hard to figure out how they could have premarital sex, because they're always living in groups).  The women, when they have their babies, give them over to the young girls to take care of.  The cook is in the kitchen doing her thing.  The young girls are out in the field, the boys are out in, you know, further fields.  So it's really group living, and it would be very difficult, I think, to do anything very sneaky.  And they are monogamous.  

The objectives of the Steinberg study, included: inbreeding effects; mother-child blood groups, linkage.  These objectives were interesting, but not particularly startling. The objectives where the living in a common environment were important were the serum cholesterol, blood pressure and so forth.  Now, I'll digress here for a moment.  We asked, I think today, what is the value of studying these specialized populations?  I told you some of the advantages; I'll tell you some of the criticisms in the Steinberg study have always been, well, “this is a unique population.  No matter what you find in this population, we can't apply it to the general population.”  Now, I think, especially with some of Dr. Ober's work lately, that's proving not to be true, but just so you know, that is a possible disadvantage of studying a specialized group.  Genetic drift was really the biggest thing that came out of the study, showing the gene variation among the different colonies.  And again, we talked today about how genetically divergent you can be within a same originating population.  So I have an originating population that splits into demes or whatever; the gene variation in those splits can be very extreme.  That's why whoever said, "Well, how can you tell much from one old skeleton?  It may have just been an outlier."  That's certainly very true, and certainly, as you mentioned, something to keep in mind.  Small sample size gives you huge variation in genes. And one of the studies I did, so you get the idea of what could be a benefit, was to study patterns of cancer.  Particularly being an inbred population, I was looking for the effects of recessive genes.  

How did we do this, and what kind of consents did we have?  Well, again, we explained the objectives to the Hutterites.  Remember, we already had all the pedigrees, so we knew who was related to whom.  We went in and we really investigated each population -- each colony, through the preacher first, and asked him, because the preachers have big books with all the family pedigrees in, and they don't have it written down, but they know the health of the whole colony.  So you sit down with the preacher, you ask about the cancer, we already had the pedigrees, and then, with his permission, we would interview the rest of the colony and confirm whose ancestors, or who themselves now had cancer or a suspicious sort of pattern of their death that would have led us to believe it might have been cancer.  We then did record searches of all the registries in Canada; as you know, they have some really nice registries.  We investigated all the death certificates, and these were all done with consent forms from the individual relatives or the person themselves.  

The advantages again are we had all the pedigrees computerized, so we already had all the genealogies, 1700s to 1980 at the time; we collected new genetic and medical data on cancer, '58 to '82; and we tested various hypotheses on the population.  Now, I have to tell you one problem which you may have already hit, is if you're trying to find death certificates and medical records in these populations that are rural, it is really difficult when you get back very far in time.  So we had a lot of uncertainty in the corresponding records.  In a lot of places, the courthouse burned down, you know, the people lost in the flood, you know, it was really incredible amounts of stories. Now, I want to just reiterate again, because I think this is something you're all thinking about if you're doing new studies, it is important to have something, I think, that is a unique identifier, which we had a FINDIV that preserves confidentiality.  Orientation number (colony of birth), we had procreation numbers (colony of marriage), this is how we identified the movement from colony to colony.

Now, we talked about preserving confidentiality.  And I have to tell you there are some other problems with this.  Carole Ober told me that recently, they published a pedigree with the family's permission.  But I guess the family didn't really see the actual manuscript before it went out, she just explained that she was going to publish their family pedigree, with the genetic disorders segregating, where you tell who the carriers were, but she said that she would disguise the pedigree, so that no one who knew them would know (1), it was their family, and (2), who in their family were the carriers.  When the paper came out, she gave the paper to the family in person, and they got very upset.  Because it turns out that although she had symbolized everybody as a little diamond so you couldn't tell the sex, and didn't say anything about what the family was or who the family was, but they knew it was a Hutterite family, and it was such a distinctive pedigree that they knew that their neighbors, if they ever saw that, in the colony, would know immediately which family it was.  And that didn't bother them as much as by the birth order, everybody in the family would know who the carriers were.  Carol was very upset at this; it was too late, the paper was out, but as we talked today about some of the times when we're trying to be confidential and preserve it, you can't always be sure you've done that.

Again, I think it's impressive what Steinberg started in the '50s. And these are just some of the studies that came out on the Hutterite population.  Eaton and Mayer was an early one.  The investigators really found the population, and that's who Steinberg heard about and went out there.  Sheps is a fertility study. Arthur Mange and Steinberg and some other did inbreeding studies.  And inbreeding is about the level of second cousins once removed, and it hasn't changed a whole lot; I guess it's going up over time, but not dramatically. 

The study I did: I traced back that there were only, at that time, 25,000 people, but they all traced back to genomes in 67 and 68 individuals, of which 44 were common, so it was a very small number of founders in this population. There are only fifteen surnames, in the population  The studies that are still in progress are HLA infertility, health profiles, for example, asthma studies and so forth.  Fertility trends are very, very much being studied at the University of Chicago.

Oh, and by the way, Dr. Ober told me that the cooperation level is so high now that the women in the colony are actually keeping their own menstrual diaries, including when they have intercourse.  She's worked with them and educated them on you know, the whole hypothesis.  So they've gotten another benefit here, real education in reproduction. She goes out and confirms data a lot, but they mail diaries to buccal her along with smears so she can get DNA analysis, and so forth.  So they really, are cooperating to the nth degree. Some of the men are questioning the women why Dr. Ober has to know when they have intercourse! 

Some of the things that Steinberg did not start out studying, and really were only added recently, are the DNA studies. And not just in Hutterites, but all of us have been talking today about what do we mean with the new genetic technology, or we wouldn't all be here today.  I mean, why is there such a big group here, why are we all we concerned about it?  It's because now, we're getting into isolating genes, not just studying patterns of genes, but actually taking them out, sequencing them, finding out in the laboratory what they do, finding out what chromosome they're on, and -- and here's the scariest part for a lot of people -- we're manipulating them.  Now, a lot of people worry about this, and you point out that humans have been breeding and altering plants and animals and, to some extent, their own populations, for eons.  The difference is it took much longer to do breeding in the field, you know, the selective mating of your pigs and your dogs and whatever, or trying to pick the right spouse for your kids, whereas now, we can actually take things and do it much faster in the laboratory, and we can mix up genes, which we couldn't do before.  I mean, you can now put a plant gene into a rat, if you have the right components, or you can move genes around.  And that, I think, is what's starting to scare people, and part of why we're here today.

People are concerned and they're confused.  You know, what does this all mean?  And I think again, that's what we're all saying: Well, what does this all mean?  We're now gong out to populations saying, give us your genes, give us your DNA. And we're saying what's going to happen to ours?  Are people going to fiddle around with my genes?  Are they going to mutate them?  One cartoon showed a more lamenting: "I had the weirdest feeling that someone was fiddling with my genes during the night."  I mean, this is not an inappreciable concern. Why is that a public concern?  We've talked about it this afternoon.  Change, any change is suspect, and then people worry you're tampering with life, and that goes along with religious objections.  And privacy invasion.  If you take a blood sample, it's maybe not so bad, but take out a blood sample and tell them you're going to look at their genes, or isolate a piece of their DNA, that starts to get scary to a lot of people.  And I think it doesn't hurt to think about it.   But there are some things that people are worried about, I think, that they haven't pinned down why they're worried, and I think it's up to groups like ours to educate the public, and ourselves, to what are the real concerns, or this is just what are some things that worry them that have no basis.

Because in this area, we are discussing today, you can see this is vague, like Skyler.  "Quick: what's nine times seven?"  "Oh, high fifties, low sixties, somewhere in there."  Teacher is not impressed.  Why not?  Skyler says, "That's what I hate about math, no gray areas."  Well the problem, I think, in the areas that we're talking about today, there's plenty of gray areas.  So the trick is to try to keep a focus on what are the factual bases. Why do we study human populations?  I think we have to remind them and ourselves! We want to ultimately benefit mankind.  Look and see what ancestors are out there in skeletons, but basically most of us want to help people and help ourselves.  First of all, you've got to do some tests, and hopefully not at the last minute, and there some limitations to lab studies where you really need to do is see what's happening in a population.  And that's the main reason we need those types of studies.
 Now I get to the part where Dr. Turner told me people may throw tomatoes at me, but that's okay, because I'm almost finished!  Will you throw transgenic tomatoes because of all the new genetic technology, we've gotten into areas where lawyers are getting involved, for the intellectual property aspects, and the ownership of property and so forth. If it was the witches of Macbeth a lot of people think about lawyers.  "The skin of a reptile, no, no heart.  He's making a lawyer!"  If you're talking now about lawyers dealing with intellectual  property, it's important to know what intellectual property is.  It's really the right of an individual, so it's a little different than what we were talking about, it's the rights of an individual relative to the community.  The rights in intellectual property can be enforced by the state, usually on an economic basis, not a criminal charge.  I mean, you violate intellectual property, you have to pay somebody a lot of money and/or stop the violations.  

Now, the patent issues are, what can you patent?  What is patenting, and how can you get at this patented technology, if you want to use it.  I'll digress here for a moment, because I was reading in one of these articles -- and I don't know if people are called Native Americans now or Indians, I'm getting a little confused.  I thought it was Native Americans, but then I think some of the people, who are members of this group got up today and called themselves Indians.  So, whatever this indigenous American group is called, I was reading, some are anti-patent, because of land patents.  So I was a little confused, and I checked into that term.  It turns out the word "patent" merely means "grant from a government of something the government can give away."  It turns out the land patents, which are still going on, were the government giving away government land (or what they thought was government land) to non-government individuals, to private individuals.  And the Indian lands which the government had given away, by land patents, were lands that originally belonged to the Indians.  Now the patents I'm talking about are not that kind, and I'm hoping they'll be clearly distinguished there.  In a way, it's simpler. The U.S. Patent and Trademark Office grants the patents.  And it grants the patent for inventions.  You have to have an invention, not a piece of land, to get a patent.  And this again, is nothing new, man has been inventing things since way back here in the caveman days.  "Hey, look at what Zog" – is a cartoon showing cavement cooking their chicken or whatever, with their hands, and Zog has his over the fire on a stick.  And this is what humans have been doing through time making technological improvements.  That's why we're all here with fancy lights and slide projectors; we keep inventing things.  

In order to protect the inventors and give them some recognition, they can write up patent applications saying, "Hey, I discovered this stick that cooks chicken over a fire without burning my hands."  It is disclosed in what's called a specification.  And I'm not getting into the details of patent law; you can see me at the bar if you really want to hear that, but claims are the things I want to mention to you.  Because people get excited when they say, "Oh, there's a patent out on a gene, or on a this or a that."  You have to, before you get excited, read the patent, and have someone tell you what these claims really cover.  For example, the Patent Office recently, and we were just talking about this at one of the biotech meetings in Chicago, the Patent Office recently decided they might allow claims for ESTs (these are little pieces of DNA that are like tags), claims that would say a DNA sequence or part of a DNA molecule including or comprising an EST.  The Patent Office would not maybe grant something saying a gene comprising EST.  Anyone in the field knows what distinction they're making, what they were worried about?  Well, if you have an EST and you say you're giving them the inventor, a claim to a gene comprising an EST, later on that inventor might say, "My patent covers the whole gene, not just the little tag sequence I found."  Whereas if you give them a claim that says the DNA fragment comprising DNA, there will be an argument that they didn't get the whole gene, because they didn't know it.  They only get that little fragment with the EST.  Now this is kind of semantic and subtle, but that's what patents are: semantic and subtle.  So before you get excited about a patent you hear about, get it, read it, or have one of your friendly patent lawyers tell you what do the claims really cover? 

How do you get these claims in a patent?  You have to have something new.  What does that rule out?  You can't go to the rainforest, pick up a plant, come back and get a patent on it.  It has to be useful, that's pretty easy.  Non-obvious is something I won't go into; it's a subtle thing that the Patent Office uses to reject everything.  And by the way, almost without fail, the Patent Office will reject the application the first time on anything that's biotechnology.  They will reject it on at least this obvious ground.  And then you have to have some lawyer argue with them that it's not obvious.  Now, you have to be careful; I remember flying out with one of my clients, an inventor from a big university, and he said he was reading the rejection from the Patent Office.  He said, "Oh yes, it's obvious!  I just put this together!" and I said "No, no, don't say that."  Because what you as scientists is "obvious," is not what the legal definition is.  You try to be modest.  I enjoy working with my clients because, and I came from science, so I know where they're coming from.  You publish a paper, you want to make it sound like, "Oh, no big deal, it was just really easy to do this."  You go to the Patent Office, because and you should, and want to say, " I had a terrible time, I had to do this, I had to do that"  In reality you forget, you've been working on this for five or six years, you forget the difficulties you had.  It's overcoming those difficulties that may get you a patent.  Because what patents are doing is rewarding inventors who have come up with something new, that's not easy to do, that's useful to society.

Now what is a patent on an invention once you get it?  It does not give you ownership of the what you claimed.  If you have a claim to a gene sequence, it does not give you ownership of the gene sequence.  What it does is it gives you the right, optional right, to keep somebody else from making, using, or selling the gene sequence.  So it's really important to keep, whatever your positions are, when you're arguing about then that it's what’s claimed that you get to protect.  You get the ownership of the patent, not the thing you claimed.  And what's in the claim is yours to optionally keep other people from making, using, or selling.  Now in reality, what does that mean?  You get a claim for a DNA sequence, you find out it's great, and you're using it in a diagnostic assay to find out if somebody's got a disease, genetic disease.  You may have then the ability to keep other people from using that diagnostic test, unless maybe you want them to pay you royalties or whatever.  Now in reality, you as the inventor have to go out usually and find some company who's going to give you some money after you've got your patent, or as you're getting your patent -- why?  Not all patents are granted, and not all patents, even you get them, are worth a hill of beans.  This is a guy who went into the Patent Office and tried to patent a “tuning spoon.”  Another near brush with fame; there's plenty of those.  

What can you patent?  You can patent a transgenic mouse, a life form, if there's some form, quality, property or combination that's new.  It has to be new.  And in 1980, the U.S. Supreme Court said, "Yes, you can patent, you can claim a microorganism that has a recombinant genetic setup that makes it equally well or more efficient than the natural kind, or than some of the other recombinants."  So in 1980, that was a turning point in biotechnology, when the U.S. Supreme Court said life forms are patentable.  And if you think that's new, they point out in their, write-up in the decision that people like Louis Pasteur had already patented a certain kind of yeast that he used that did a better job in brewing, so there are all kinds of interesting old patents.   The Human Genome Project is trying to patent these various things: DNA segments, enzymes, transgenics, probes, vectors.  You can patent a method or computer software. Now, I said that the patent doesn't give you the right to own the thing you claim, it only gives you the right to keep others from using it.  In the U.S., not in the other countries, but in the U.S., the inventor has the first ownership of the patent.  If the inventor wants to give up that ownership -- of the patent now, not of the invention -- he or she can assign it.  Now, usually you're working for a university, so you have to assign it to the university.  If you're working for a company, you have to assign it to the company.  If you're an independent inventor, you should assign it to somebody, because otherwise you're not going to have the money to follow up on it if you do want to do that.  Now some scientists say, "Well, I never want to benefit from this patent, I don't want to sell it to a company, I don't want to do anything."  Remember, what it's giving you is control.  You don't have to enforce the patent, but when it's out there, everybody knows they better not make, use or sell that, or they risk your coming after them.  So even if you don't exploit it, you can keep other people from practicing your invention.  And sometimes inventors want to do that, because they're afraid of what other people will do with their discovery.  So there are many reasons to get a patent.

Well, the U.S. Constitution provided patents to give economic incentives for people to invent and not hide the invention and to give inventors recognition. The provision in the Constitution, was to encourage people who at the time were keeping a lot of stuff secret. This way, you reveal the patent, and it's up to the other people to then go further.  You get a gene, you figure out what to do with it in the next patent.  I said you don't have to enforce it.  You can have this beautiful patent, it looks very pretty, you don't have to do anything.  If you want to do something, you would sue people for infringement, you say, "You're using, making or selling my claimed item."  You can get damages, which is money, or you can tell them to stop. I know this is kind of dry, nothing like ending up with a legal session.

So again, just to reiterate: you can patent methods, you can patent compositions, organisms, whatever.  But they have to be new, useful, and non-obvious.  Now the big question is again: should genes be patented?  One thing you have to think about is how to define a gene, and there’s the little distinction I told you the Patent Office was making. 

A complex but useless invention may get a lot of research grants!  We all wish we had some kind of apparatus like this!  And this is the kind of thing you can't patent.  You can't patent something that doesn't have a use.  Those of you who follow the argument with the NIH ESTs and so forth, remember that was one of the big arguments, that they had no use.  The Patent Office since then has really loosened up.  If you can show any use that is credible, but is not totally crazy, this criterion will be satisfied.  You don't have to show that it cures cancer, you can just say it's something that would be a diagnostic test.  You don't have to say it really works!  What's going to happen if your patent doesn't work?  Well, nobody's going to bother with it, nobody's going to replicate it, so nobody cares.  And that's what the Supreme Court said to the Patent Office: you're not the FDA, it's not up to you to decide whether inventions work.  It's only up to you to say that the invention has credible use.

Now, people worry, should we patent these DNA sequences?  And you've all heard, these fights that are still going on.  It's important to remember that it's only patentable if it's new, if it's made by humans.  You can't just say, "I'm going to look at you and I'm going to patent your genes," and you can't do that, okay?  And if I do patent a gene that happens to be in your body, the gene sequence is patented is isolated, that doesn't mean you're infringing my patent!  You're not making, using or selling that isolated or cDNA, which isn't found in nature, or the piece of DNA in something -- it has to be something that man did.  That's what the Supreme Court says: anything made by the hand of man under the sun is patentable.  So it has to be something not in nature.

Now, those of us who feel something should be patented say sure, if it fulfills the criteria, it's something that's hard to get, if it's a benefit for society, a patent is going to give you the ownership, then it allows companies to have some protection taking that gene sequence or whatever further, making gene therapy methods, finding anti-SENSE to turn off the gene, making probes to DIAGNOSE the disease. There are those of us, and I know, not everybody, who don't believe this restricts dissemination or availability.  Why?  The minute you've got your patent application filed.  You don't have to wait for the patent to issue.  It's filed; you can publish.  And the DNA sequences are out there.  Now, it's up to people to take that information that's now disseminated and do other things with it, even though we've got a claim to that sequence.

In a cartoon, a lover says, "Marry me.  My genes are excellent and not yet patented!"  This is a little misconception, because he's again thinking that his genes could be patented, and his genes, as they exist in him, in the aggregate, cannot be patented.  You all know also that there is a statutory provision against "slavery," so you can't patent a human being.  Now, some of us have wondered, well, if you keep putting animal genes into human, could we eventually get something that's sort of more on the side of the human?  I think that's pretty far-fetched, because of all the internal controls on human evolution.  It would take you a long time, I think, to replicate something like a human, but it's a thought.  

Now, just a word about transgenics.  In a cartoon, a woman said, "Well, I didn't mean to kill him; I just hit him with one of the new genetically transgenic hard tomatoes." And you've all heard of the Colgene tomato, which has some transgenic controls so that tomatoes didn't rot after you picked them off the vine.  That's not done very well, but it was one of the first transgenic plants, and they have advantages.  There are a lot of other things coming out that might do better.  As I understand it, one of the problems was chefs didn't like the tomato, who knows why, and the other reason is they couldn't grow enough of them in all these different zones to commercially produce enough to feed the market.  We also have transgenic animals. What's good about this? One of the advantages of the transgenic animal, and this has shocked me.  One of my inventors at the University of Illinois, and this is not confidential because our patents are out, is working in the area of pig transgenics.  I went down there to look at the pigs and to see why we're doing this.  The inventor explained to me that these would be good for xenografts, creating pancreases and livers and all this stuff for transplant into humans.  And I looked at this big, ugly pig, which was a Meishong Chinese pig crossed with one of our kinds of domestic pigs, and I said, "Why are we using pigs?"  And he said, "Because pigs are the closest animal to humans, in terms of organ size and immunology."  I looked at this animal, and really was humbled.  

But anyway, transgenic’s moving along.  Companies are looking at these pancreases that shouldn't because they've got human genes in now, and they shouldn't have the transplant problems, because they're basically trying to put some of our immune genes in there.  This pancreas won't react as strongly if they transplant it into a human. That would be beneficial. Of course, there are people who don't believe in transplants on religious grounds.  And a lot of people think that genetic programming is saying, :"My genetic programming prevents me from stopping to ask directions."  Well, I think we all have traveled with people like that.  My parents drove around Boston for hours trying to get off the freeway because my father would not ask directions!  But again, I think we have to remember when people start worrying about this determinacy, that your phenotype or your outward appearance, your inner appearance, whatever, is not just your genes, but a result of your environment and other genes that are present.  So you've got to keep the complexity in mind.  

Finally, one of the successful outcomes that we're all hoping for is gene therapy, to actually correct the, defect not to just get rid of people with any kind of defective gene, or not have them born, but to actually correct the defect by introducing new genes.  As you know, gene therapy is going on now for some selective diseases, and my feeling is that in the future, at least for some the single genes, they will have a lot of therapies.  I think I've given you a little hint of my experiences with things that affect what you've all been concerned about.  I certainly have learned a lot from all of the talks today, and the conversations -- and I certainly will take, I guess a few questions.  I will also be probably hanging around here for a while, if anyone wants to get into more detail in patent law, Hutterites, or anything else.  Any questions here?  

Q: Can you explain the difference between the sort of control that a patent gives you, and ownership?  You made a point of making that distinction.

Martin: Sure.  Well, that's a good question.  Ownership. Let's say that you own your land, that your house is on.  That means that you can do anything you want with that land, within the law.  It's yours.  It belongs to you, you can pass it on to somebody else, you can keep other people off the land, just like with a patent.  But it's something that actually belongs to you, you can will it to people, it's a thing that belongs to you.  A patent only gives you the right to keep -- well, if you use the land analogy, you don't really own your land, but you could keep people from using your land.  You can keep them off -- it's more like a rental, you keep them off, but it doesn't give you ownership of the land.  You can't pass it on, you don't have title to it, you can just keep other people off.  

Q: You can't destroy it or...

Martin: You can't destroy it, no.  Then you'd hit other kinds of laws, perhaps.  

Q: The time limit on a patent?

Martin: The time limit on a patent right now is 20 years from the day you file the patent application.  Those who may have patents from the past, it used to be 17 years from the day you got the patent.  And by the way, it usually takes years to get a patent through the Patent Office unless you've got some Nobel Prize-winning invention.  So now it's 20 years from the day you file it, which means you want to hurry up to the Patent Office so you don't lose time.

Q: You made one very interesting point --

Martin: Only one?  

Q: That the people that you talked to still enter the data into the genome database when they file a patent application.  And that was one of the big concerns at the beginning. I'm glad that's not happening.

Martin: It doesn't seem to be happening, if for no other reason then, if you want to publish it, then most of the journals now make you put it in the computer database.  Plus the other reason you want to hurry up and put it in there is you want to keep your priority -- you want to stake out your turf, to this, "I found this.  It's mine to control."

Q: It reinforces the discovery.

Martin: Right, reinforce your discovery.  Now, we've had some odd things.  Like one of my inventors, the day we filed the patent, or the day before we filed the patent, unbeknownst to us, someone published in the gene database, in Japan, the cDNA.  We had a cDNA and a genomic DNA.  They only published the cDNA.  Well, of course, we didn't realize this, because we checked there, but you usually don't check the day before you file a patent.  So the examiner found it and said, "Oops, you can't have the DNA, somebody else has it out there."  And what we were able to do was convince him, which I think was a good argument, that we should at least get the genomic sequence, because you couldn't predict the genomic one, from the cDNA.  And there was some value to making diagnostics and things from use of the genomic molecule.  So patenting is a very tricky business; it's not an easy thing.  

By the way, it does discriminate, the system does discriminate against the individual inventor.  This is an expensive procedure if you don't have backing from a university or from a company, or private money, which some people do, it may be possible to obtain, but neither commercialize nor protect your invention.  I think that is a flaw in the system, a lot of us have talked about that.  There's patent office fees that are expensive, there's filing fees, attorneys.  You can write it yourself, you don't need an attorney, and the patent office gives you special consideration, but usually in biotech, you need to hire an attorney. Then you argue with the Patent Office, that costs money.  To sue somebody for infringement is astronomically expensive.  To file in foreign countries, you have one year from the day you file here to file in most foreign countries.  To do that, I mean, I just had an inventor who didn't get somebody to back her.  She got up to the stage where we now have to go in the individual country, it's a deadline, and she had to come up with about  $50,000.  And that's not anything in the U.S.:  we're just paying all these different offices around the world.  Their fees, their translation fees, are what run this bill up.  In Japan, one of my inventors -- he had backing, so he could do it – spent almost $25,000 to have his patent application translated into Japanese.  And that's not unusual.  And you can't do it yourself.  You have to use the accepted translators.  You think it's bad in the U.S., well, you try to go around the world, and it's really expensive.  The problem is, if you don't go around the world, and you've really ended up with something good, you pass that deadline, and then other people in other countries can just make it at will, and steal your markets.

Q: Let's say you're a geneticist and I'm a subject, and you take my blood and you work on it, and find some cDNA, and you file a patent on it.  You don't own my DNA, but you have some sort of rights to it.  You could make a lot of money off it, which I can't, because I don't have any right to what you've done on my cells.  But on the other hand, you couldn't have done it without me.  And it stands to reason, that, in my mind, that's a heck of an altruistic act on my part, to have allowed you to do your research, with my participation, even though I'm not going to get anything out of it.  I guess my question is, what is my incentive for allowing you to start that process, by taking my blood and working on my genes?

Martin: Well, of course I think the consent form should make clear that somebody could take these things and get a patent on them and eventually there would be some money coming out of it.  Which would mean if you don't want to participate, you have to refuse.  This is that Iceland story again too.  They certainly may make money off products developed from genes.  The incentive for you is often just altruistic, really, or you're getting something else out of it, you know, some medical attention, or some people just like to be in studies.  Some people think as, I guess, the Aleutians feel with the ancient DNA, well, no big risk, no big benefits to me right now, so who cares.  Now, the more intrusive the way of getting something from you, the more the concern.  You're probably familiar with the story of the guy whose spleen was used to derive a very famous cell line.  He sued in California the company making money.  And the court very strongly said, and this has been held up several times, that you don't own the rights to anything that's taken out of your body.  That's just where we are.  Which means that people should know that, so that if they don't want something taken out of their body, or if you want you can make a deal.  I mean, you can always make some kind of deal with the investigators, if they want something from you badly enough.  They might not agree, but if you're free to negotiate with them.  There have been, I know, people who've gotten paid for things.  Not necessarily royalties usually, a lump sum.

Q: . . . but then this leads to when you're filing your patent application, do you have identify what it came from?  And I'm just thinking, I just went through having a baby, and I cross off everything.  I say no, no, no pictures, no samples, no anything.  You know, even though I was being drugged.  But does that mean, I mean, but then yet, my stuff is out there, and I will know what happened to me?

Martin: Well, it is a worry.  We all, I think, are worried about the confidentiality of samples that are taken from people.  I mean, that's almost a separate issue, and that is a big concern.  For example, the government, as you've been probably reading would like to have all of us DNA tested, and our names would be associated with the DNA.  I think most of us are very leery about that!  I mean, they can give all the reasons they want, but it smacks a little too much of Big Brother.  When you get the patent, you have to tell people how to practice your invention.  That's part of the bargain you're making with the public.  So you would have to say how you got this DNA sample, but you don't have to say who it came from, because that's not important for people trying to replicate it.   They don't have to go back and get your blood sample, because you have now told them what the sequence is, and how to get it.  So they don't need now to go back to you.  All they have to know is basically in general the sources, it's called enablement.  You have to enable -- so if you pick up my patent, and you read it, you have to be able to go and do what I did.  But you don't have to do it exactly the same way.  You don't have to go out and find your blood again.  As long as you can do what I claim.  If I claim a sequence, and I tell you what the sequence is, you can do it yourself in several different ways.

Q: I like what George says about the Morris case.  He paraphrases Naomi and says only the can own cells.  Basically, everybody else can own cells, with or without informing the patent.  In Morris' case, he gave them consent.  But I wanted to go back to the question of a life patent.  Just because you have the PTO issuing life patents doesn't make it right.

Martin: What do you mean?

Q: Just because you isolate, you know, a genetic characteristic within a living genome, you didn't invent it.  And I think it's just a slippery slope that is probably taking... The U.S. is leading the way in this, and it's now become very well established through international superstructures, economic superstructures,  and so on.  But I still don't believe it's right.  I think that a lot of countries in the world are trying to stop it.  The European countries are, for sure, continue to hotly debate it in both directions.  And so I'm just saying that there's no way that any scientist in this room can claim to have invented a natural, biological process, and the isolation or the copying of that DNA sequence really still doesn't mean that they made it.

Martin: Well, you must clearly define what an invention is.  An invention means that the hand of man took something natural and altered it.  In your body, there is no cDNA.  It does not exist.  So if you patent, which most of the genes are, in the form of cDNA, that's not in your body.  Somebody did invent that and isolate it in the lab.  And if you take an isolated fragment of a genomic DNA, you had to remove that and you have to sequence it.  It's not a natural thing, because there is no such thing as an isolated genomic piece in your body or any other plant or animal body.  There is no such entity.  It has to be intervened by the hand of man.  And it's, when, you know, you talk about the European countries, they're actually allowing genes to be patented now, and when you try to pin people down, well what is the downside of allowing a patent on this sequence?  Nobody yet has been able to give me a reason except a religious reason.  Nobody's been able to give me a reason why this is going to be detrimental to either individuals or populations.

Q: I remember reading a story at one point about a famous cell line, and you know, the one aspect of that was that -- this is a cell line, I'm not going to remember the history probably as well as some people.  But the one aspect of that was that in one sense, the person, in a sense, who donated the cell line without her knowledge, and she died of ovarian cancer, I think it was ovarian cancer, is that what it was?  But the interesting thing about that, about the legacy of that story, was that her cell line, which then continued to grow over tens of years, began to be identified by her.  And some creepy aspect of this was that racial characteristics were being applied to the cell line, and gender characteristics were being applied to the cell line.  Because the cell line, one of the things that it, you know, that began to be said about it, was that you know, it had a sort of a lascivious nature, that it would infect other cell lines, and that it was, because it get into, had this quality of getting into other things, someone else is going to have to do?  But there was a quality to this in which specifically racial and specifically gender characteristics started to be applied to this cell line because of the woman who it had been associated with.  So there were some weird aspects of this...

Martin: I have to say, I've never heard -- I mean, I know the cell line, and it's an immortal cell line, as many of the cancer cell lines are, and it grows forever, but I've never heard this story. Anyone else know that story?  I don’t' have any recollection of a lascivious cell line.

Q: Well, a paper will be published presently, and a book that's coming out in the Center, that's why I know.  I have to edit it in about three days now, and I remember when it was given, at a conference on biotechnology at the Center two years ago, and there was, there was something very disturbing about that story.

Martin: Yeah, I'd like to see the book.  I knew the cell line got contaminated from other cells over time, so when they finally checked it out, the cell line these people were all using wasn't really the same cell line they started out with, but I never knew...  Anything else?

Q: How are people defining genes?

Martin: Well, Dr. Steinberg told me a gene was a section of DNA that encoded a single message or polypeptide chain or, you know, peptide.  And so it was an entity that acted as a unit under control of a regulatory [inaudible], and produced something that was identifiable and discreet.  I think nowadays there's a lot of argument about what a gene is.  To me, that's still a good definition of a gene, as distinct from -- it's an operational unit -- as distinct from just a piece of DNA.  And you know we've got tons of DNA floating around, and we can't tell if it does anything.  So I think the word "gene," and the reason the Patent Office has gotten sticky, I think with good reason, if you don't have possession of the gene, you haven't really taken it out, and you send in a patent application, which people are doing.  They say, "I claim the gene for high cholesterol,” whatever.  Okay?  People were starting to get some claims to patents like that.  But when you think about it, any of us could then sit down and write a patent and say, "I claim the gene for this, I claim the gene for that,"  you know, it would be ridiculous because you didn't really invent it.  So now the PTO is cutting down, where you have to prove possession of the gene, and the reason they're pushing sequences as opposed to just saying you showed a gene in a family, is to prove that you actually have the gene in your laboratory.  You have the sequence, or if it's a whole gene, you have the whole gene.  Now, the problem with that is the Patent Office is now only giving you the molecule with the sequence you actually worked with.  Now, a competitor comes up and says, "Gee, that's a great patent, I'm going to just change a few nucleotides over here, I'll still get a functional protein, and I'll claim that."  And so what you're ending up with is a lot of people with claims to essentially similar things, which in some cases is going to block anybody from using any of it, probably, which is kind of a standoff.  

Q: I guess I'm still not clear on --

Martin: A gene is a DNA molecule, okay?

Q: No, no, I have another one.

Martin: Oh!  Okay, okay.  Well, I have to tell you, I lectured to the law students at Marshall one time, and it was when the O.J. Simpson trial was coming on.  You know, there was so much about DNA testing and that.  And these are guys who are probably in their mid-20s, they already had their law degrees, so I kind of figured they all knew about DNA, and that DNA molecule I showed you?  I just showed that, and then I went on with all this case law, and all this.  And they're all looking at me, and finally I said, "You do all know about DNA, you know, and genes, and all that?" and they shrugged.  So I had to go back and try to explain DNA, and I said, "Well, if you have any questions, wave at me."  So one guy waved at one point and he said, "Could you explain patenting a DNA sequence in terms of patenting a bowling ball?"  And I'm rarely at a loss for words, but...  [laughter]  So the next year I went back, I started with basic genetics, and I went through the whole thing.  But that didn't answer your question.  Go ahead, that's a digression.

Q: So when someone submits a patent for a gene, are they saying this is an original sequence?

Martin: Well, see, you can't anymore even try to say a gene for whatever, without having either some way... See, what happens in your claim, you have to make it so that if someone picks up your patent, he/she knows if what he/she's doing would infringe your patent.  So if just say a gene for something, and you don't give its characteristics, you don't give its sequence, and you don't give how you isolated it, you can't get that claim.  That's not a patentable claim.  

Q: So people can't say, "Here's a bat, and I want to patent the sequence contained in this bat."  You can't do that?

Martin: No, although in the which?

Q: Or some kind of vector...

Martin: If you deposit the vector in a depository like the ATCCC, and you say, I'm claiming this vector with this ATCCC number, even if you didn't have time to sequence it, there's some argument whether you can get -- you can probably get a claim to that vector you deposited in an E. coli or something.  If somebody else later came along and found the sequence, that's where the argument begins.  Do they also get a claim to the sequence when you've got the vector sitting there?  That's an arguable point right now, that' s not resolved.  A lot of these things are not resolved yet.  One more?

Q: I had a question.  I was wondering about this.  It's kind of an absurd example, but under the criteria for patenting, novelty, hands-on, couldn't two parents put a patent on their child because it's a novel, unique, it's never been made before?  Certainly, man was involved in this process... as a child, you can't touch it, is that possible?

Martin: Well, number one, by our Constitution, you can't patent a human being, even if that were satisfying the other patentability criteria.  And I think that the Patent Office would go back and argue, even if that were the restriction, is that it would be obvious, that everybody can do this sort of think, you know! But I think it's a good thing to think about.

Q: Well, I was wondering then, because if the Indians patent all their kids, that would solve a lot of problems.  

Martin: Yeah, right now you can't do that.  You can't even patent your animals, unless they are something that you, you know, made special.  You can patent, by the way, and I have, plants that you made by breeding experiments that come out to be new plants.  I mean, we've done that for years.  Corn, for example. Thank you.